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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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Wong ML, Widerström-Noga E, Bolanos JL, Gonzalez G, Penedo FJ, Hosein PJ, Tovin MM, Gonzalez JP, McTeague LM. Feasibility of trancutaneous auricular vagus nerve stimulation in Black and Hispanic/Latino people with peripheral neuropathy. FRONTIERS IN PAIN RESEARCH 2025; 5:1516196. [PMID: 39896735 PMCID: PMC11782131 DOI: 10.3389/fpain.2024.1516196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 12/31/2024] [Indexed: 02/04/2025] Open
Abstract
Introduction Peripheral neuropathy (PN) is the most common neurodegenerative disorder, and the primary causes are chemotherapy-induced peripheral neuropathy (CIPN) and diabetic neuropathy (DN). Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising non-pharmacological and non-invasive intervention that targets key pathways involved with PN. However, research is needed to determine the feasibility, acceptability, and effects of taVNS in people with PN. It is also critical that this research on taVNS include the perspectives of Black and Hispanic/Latino patients, who are often underrepresented in research. Methods This research was comprised of two consecutive studies: a survey and a pilot randomized sham-controlled trial (RCT). The survey assessed symptom burden, management strategies, and interest in taVNS among CIPN patients. The pilot RCT evaluated the feasibility, acceptability, and preliminary effects of taVNS in Black and Hispanic/Latino patients with CIPN or diabetic neuropathy. Participants were recruited from the University of Miami medical system, with culturally sensitive approaches to enhance minority participation. Results The survey included 62 respondents, 78% Black or Hispanic/Latino, revealing high symptom burden and significant interest in taVNS (82% expressed moderate to high interest). The pilot RCT enrolled 28 participants, achieving a 42% recruitment rate and 86% retention. taVNS was well tolerated, with no significant adverse effects. Preliminary data indicated a decrease in neuropathic symptoms and an increased heart rate variability (HRV) during active taVNS, suggesting autonomic modulation. Tingling sensation and pain decreased by median values of 2.0 and 1.5, respectively. Additionally, the median values for standard deviation of the RR interval increased from 34.9 (CI = 21.6-44.8) at baseline to 44.8 (CI = 26.5-50.3) during intervention. Exit interviews highlighted positive participant experiences and identified potential barriers, such as protocol length and distrust in medical research. Conclusion The findings underscore the need for novel CIPN treatments and demonstrate the feasibility of conducting taVNS research in historically underrepresented populations. High interest in taVNS and successful recruitment and retention rates suggest that culturally sensitive approaches can enhance minority participation in clinical trials. These findings will be used to develop a large clinical trial to determine the efficacy of repeated taVNS in a diverse cohort. Clinical Trial Registration https://clinicaltrials.gov, identifier (NCT05896202).
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Affiliation(s)
- Marlon L. Wong
- Department of Physical Therapy, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Eva Widerström-Noga
- The Miami Project to Cure Paralysis, University of Miami, Miami, FL, United States
| | - Jessica L. Bolanos
- Department of Physical Therapy, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Gabriel Gonzalez
- Department of Physical Therapy, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Frank J. Penedo
- Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Peter J. Hosein
- Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Melissa M. Tovin
- Department of Physical Therapy, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Juan P. Gonzalez
- Department of Physical Therapy, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Lisa M. McTeague
- Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, United States
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Bhrigu B, Sharma S, Kumar N, Banik BK. Assessment for Diabetic Neuropathy: Treatment and Neurobiological Perspective. Curr Diabetes Rev 2025; 21:12-31. [PMID: 38798207 DOI: 10.2174/0115733998290606240521113832] [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: 01/26/2024] [Revised: 04/01/2024] [Accepted: 04/19/2024] [Indexed: 05/29/2024]
Abstract
Diabetic neuropathy, also known as diabetic peripheral sensorimotor neuropathy (DPN), is a consequential complexity of diabetes, alongside diabetic nephropathy, diabetic cardiomyopathy, and diabetic retinopathy. It is characterized by signs and symptoms of peripheral nerve damage in diabetes patients after ruling out other causes. Approximately 20% of people with diabetes are affected by this painful and severe condition. The development of diabetic neuropathy is influenced by factors such as impaired blood flow to the peripheral nerves and metabolic issues, including increased polyol pathway activation, myo-inositol loss, and nonenzymatic glycation. The present review article provides a brief overview of the pathological changes in diabetic neuropathy and the mechanisms and types of DPN. Various diagnostic tests and biomarkers are available to assess nerve damage and its severity. Pharmacotherapy for neuropathic pain in diabetic neuropathy is complex. This review will explore current treatment options and potential future developments to improve the quality of life for patients suffering from diabetic neuropathy.
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Affiliation(s)
- Bhanupriya Bhrigu
- Department of Pharmaceutical Science, Lords University, Alwar, 301028, Rajasthan, India
| | - Shikha Sharma
- Department of Pharmaceutical Science, Lords University, Alwar, 301028, Rajasthan, India
| | - Nitin Kumar
- Department of Pharmaceutical Science, Lords University, Alwar, 301028, Rajasthan, India
| | - Bimal Krishna Banik
- Department of Mathematics and Natural Sciences, College of Sciences and Human Studies, Prince Mohammad Bin Fahd University, Al Khobar, Kingdom of Saudi Arabia
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Bromberg T, Gasquet NC, Ricker CN, Wu C. Healthcare costs and medical utilization patterns associated with painful and severe painful diabetic peripheral neuropathy. Endocrine 2024; 86:1014-1024. [PMID: 39001927 PMCID: PMC11554691 DOI: 10.1007/s12020-024-03954-6] [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: 11/27/2023] [Accepted: 07/02/2024] [Indexed: 07/15/2024]
Abstract
PURPOSE Painful diabetic peripheral neuropathy (DPN) is a common complication in patients with diabetes. It is associated with a poor quality of life and high costs of care. This study investigated the impact of painful DPN on healthcare costs and resource utilization. METHODS This was a retrospective analysis of administrative claims of adult patients with diabetes (type 1 or 2) from Optum's de-identified Clinformatics® Data Mart Database. Patients were assigned to four cohorts by presence of DPN and pain severity, based on diagnoses and prescription patterns in a one-year baseline. All-cause and diabetes-associated costs were calculated for the year following the index DPN diagnosis. Risk factors associated with presence of severely painful DPN were evaluated. RESULTS Relative to those without DPN, patients who had DPN without pain, painful DPN (PDPN), or severe PDPN incurred respective increases of $3,093, $9,349, and $20,887 in average annual all-cause costs. More than half of costs from painful/severe DPN were for prescriptions and inpatient hospitalization. Severe PDPN was associated with elevated odds of diabetic amyotrophy (OR: 8.09; 95% CI: 6.84-9.56), diabetic foot ulcers (OR: 6.54, 95% CI: 6.32-6.76), and loss of mobility (OR: 2.54, 95% CI: 2.48-2.60), among other complications. CONCLUSIONS Painful DPN is associated with higher healthcare costs and resource utilization, and a greater risk of debilitating conditions that limit quality of life. Future research should focus on better treatment options and more aggressive pain management strategies to reduce the negative impacts of DPN.
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Affiliation(s)
- Todd Bromberg
- Delaware Valley Pain & Spine Institute, Chalfont, PA, USA.
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Yu Z, Zhao S, Cao J, Xie H. Analysis of risk factors for painful diabetic peripheral neuropathy and construction of a prediction model based on Lasso regression. Front Endocrinol (Lausanne) 2024; 15:1477570. [PMID: 39502564 PMCID: PMC11534718 DOI: 10.3389/fendo.2024.1477570] [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: 08/08/2024] [Accepted: 09/30/2024] [Indexed: 11/08/2024] Open
Abstract
Objective To evaluate the prevalence and risk factors of painful diabetic peripheral neuropathy (PDPN) in patients with type 2 diabetic peripheral neuropathy (DPN) in Hunan Province, and establish and verify the prediction model. Methods This was a retrospective study involving 4908 patients, all patients were randomly divided into the training dataset(3436 cases)and the validation dataset (1472 cases) in a ratio of 7:3. Electroneurogram, clinical signs,and symptoms were used to evaluate neuropathy. Least absolute shrinkage and selection operator (LASSO) regression was used to select the optimal factors, and multifactorial logistic regression analysis was used to build a clinical prediction model. Calibration plots, decision curve analysis (DCA), and subject work characteristic curves (ROC) were used to assess the predictive effects. Result The prevalence of PDPN was 33.2%, and the multivariate logistic regression model showed that peripheral artery disease, duration of diabetes, smoking, and HBA1c were independent risk factors for PDPN in patients with type 2 diabetes. ROC analysis results showed that the AUC of the established prediction model was 0.872 in the training dataset and 0.843 in the validation dataset. The calibration curve and decision curve show that the model has good consistency and significant net benefit. Conclusion 33.2% of DPN patients had PDPN in Hunan Province, China. Peripheral artery disease, duration of diabetes, smoking, and HBA1c are risk factors for PDPN in patients with type 2 diabetes. The prediction model is based on the above factors, which can well predict the probability of PDPN.
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Zhang EX, Yazdi C, Islam RK, Anwar AI, Alvares-Amado A, Townsend H, Allen KE, Plakotaris E, Hirsch JD, Rieger RG, Allampalli V, Hasoon J, Islam KN, Shekoohi S, Kaye AD, Robinson CL. Diabetic Neuropathy: A Guide to Pain Management. Curr Pain Headache Rep 2024; 28:1067-1072. [PMID: 38967712 DOI: 10.1007/s11916-024-01293-9] [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] [Accepted: 06/25/2024] [Indexed: 07/06/2024]
Abstract
PURPOSE OF REVIEW Diabetic neuropathy is a common complication of diabetes mellitus (DM) and can affect up to 50% of DM patients during their lifetime. Patients typically present with numbness, tingling, pain, and loss of sensation in the extremities. Since there is no treatment targeting the underlying mechanism of neuropathy, strategies focus on preventative care and pain management. RECENT FINDINGS Up to 69% of patients with diabetic neuropathy receive pharmacological treatment for neuropathic pain. The United States Food and Drug Administration (FDA) confirmed four drugs for painful diabetic neuropathy (PDN): pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch. Nonpharmacological treatments such as spinal cord stimulation (SCS) and transcutaneous electrical nerve stimulation (TENS) both show promise in reducing pain in DM patients. Despite the high burden associated with PDN, effective management remains challenging. This update covers the background and management of diabetic neuropathy, including its epidemiology, pathogenesis, preventative care, and current therapeutic strategies.
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Affiliation(s)
- Emily X Zhang
- Department of Anesthesia, Critical Care and Pain Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA
| | - Cyrus Yazdi
- Department of Anesthesiology, Critical Care, and Pain Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Rahib K Islam
- LSU Health Sciences Center New Orleans School of Medicine, 1901 Gravier Street, New Orleans, LA, 70112, USA
| | - Ahmed I Anwar
- Department of Psychology, Quinnipiac University, 275 Mt Carmel Ave, Hamden, CT, 06518, USA
| | - Alana Alvares-Amado
- American University of the Caribbean School of Medicine, 1 University Drive at, Jordan Dr, Cupecoy, Sint Maarten
| | - Horace Townsend
- American University of the Caribbean School of Medicine, 1 University Drive at, Jordan Dr, Cupecoy, Sint Maarten
| | - Kaitlyn E Allen
- LSU Health Sciences Center New Orleans School of Medicine, 1901 Gravier Street, New Orleans, LA, 70112, USA
| | - Elena Plakotaris
- LSU Health Sciences Center New Orleans School of Medicine, 1901 Gravier Street, New Orleans, LA, 70112, USA
| | - Jon D Hirsch
- Department of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, 71103, USA
| | - Ross G Rieger
- Department of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, 71103, USA
| | - Varsha Allampalli
- Department of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, 71103, USA
| | - Jamal Hasoon
- Department of Anesthesia and Pain Medicine, UTHealth McGovern Medical School, Houston, TX, USA
| | - Kazi N Islam
- Agricultural Research Development Program, Central State University, 1400 Brush Row Road, Wilberforce, OH, 45384, USA
| | - Sahar Shekoohi
- Department of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, 71103, USA.
| | - Alan D Kaye
- Departments of Anesthesiology and Pharmacology, Toxicology, and Neurosciences, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, 71103, USA
| | - Christopher L Robinson
- Department of Anesthesiology, Critical Care, and Pain Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA
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Hernando-Garijo I, Medrano-de-la-Fuente R, Mingo-Gómez MT, Lahuerta Martín S, Ceballos-Laita L, Jiménez-Del-Barrio S. Effects of exercise therapy on diabetic neuropathy: A systematic review and meta-analysis. Physiother Theory Pract 2024; 40:2116-2129. [PMID: 37341684 DOI: 10.1080/09593985.2023.2227975] [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: 03/02/2023] [Revised: 06/01/2023] [Accepted: 06/01/2023] [Indexed: 06/22/2023]
Abstract
OBJECTIVE To evaluate the effects of exercise therapy on neuropathic symptoms, signs, psychosocial aspects, and physical function in people with diabetic neuropathy (DN). METHODS A search in PubMed, Web of Science, Physiotherapy Evidence (PEDro), and Cochrane databases was performed from inception to Invalid Date NaN, . Randomized clinical trials (RCTs) were selected in patients with DN comparing exercise therapy with a control group. The studies' methodological quality was assessed with the PEDro scale. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the overall quality. RESULTS Eleven RCTs (n = 517 participants) were included. Nine studies showed high methodological quality. Mean (MD) and standardized mean differences (SMD) were observed in favor of exercise therapy for symptoms (MD = -1.05; confidence interval 95% = -1.90 to -0.20), signs (SMD = -0.66; confidence interval 95%= -1 to -0.32), and physical function (SMD = -0.45; confidence interval 95% = -0.66 to -0.24). No changes were found in psychosocial aspects (SMD = -0.37; confidence interval 95% = -0.92 to 0.18). The overall quality of evidence was very low. CONCLUSION The quality of evidence suggesting that exercise therapy provides short-term benefits in neuropathic symptoms, signs, and physical function in patients with DN is very low. Furthermore, there were no effects found on psychosocial aspects.
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Affiliation(s)
- Ignacio Hernando-Garijo
- Faculty of Health Sciences, University of Valladolid, Soria, Spain
- Clinical Research in Health Sciences Group, University of Valladolid, Soria, Spain
| | - Ricardo Medrano-de-la-Fuente
- Faculty of Health Sciences, University of Valladolid, Soria, Spain
- Clinical Research in Health Sciences Group, University of Valladolid, Soria, Spain
| | - María Teresa Mingo-Gómez
- Faculty of Health Sciences, University of Valladolid, Soria, Spain
- Clinical Research in Health Sciences Group, University of Valladolid, Soria, Spain
| | | | - Luis Ceballos-Laita
- Faculty of Health Sciences, University of Valladolid, Soria, Spain
- Clinical Research in Health Sciences Group, University of Valladolid, Soria, Spain
| | - Sandra Jiménez-Del-Barrio
- Faculty of Health Sciences, University of Valladolid, Soria, Spain
- Clinical Research in Health Sciences Group, University of Valladolid, Soria, Spain
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Junquera-Godoy I, Martinez-De-Juan JL, González-Lorente G, Carot-Sierra JM, Gomis-Tena J, Saiz J, García-Blasco S, Pertusa-Mazón I, Soler-Climent E, Prats-Boluda G. Muscle Network Connectivity Study in Diabetic Peripheral Neuropathy Patients. SENSORS (BASEL, SWITZERLAND) 2024; 24:4954. [PMID: 39124001 PMCID: PMC11314729 DOI: 10.3390/s24154954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 07/26/2024] [Accepted: 07/29/2024] [Indexed: 08/12/2024]
Abstract
Diabetic peripheral neuropathy (DPN) is a prevalent complication of chronic diabetes mellitus and has a significant impact on quality of life. DPN typically manifests itself as a symmetrical, length-dependent sensorimotor polyneuropathy with severe effects on gait. Surface electromyography (sEMG) is a valuable low-cost tool for assessing muscle activation patterns and precise identification of abnormalities. For the present study, we used information theory methods, such as cross-correlation (CC), normalized mutual information (NMI), conditional granger causality (CG-Causality), and transfer entropy (TE), to evaluate muscle network connectivity in three population groups: 33 controls (healthy volunteers, CT), 10 diabetic patients with a low risk of DPN (LW), and 17 moderate/high risk patients (MH). The results obtained indicated significant alterations in the intermuscular coupling mechanisms due to diabetes and DPN, with the TE group showing the best performance in detecting differences. The data revealed a significant increase in information transfer and muscle connectivity in the LW group over the CT group, while the MH group obtained significantly lower values for these metrics than the other two groups. These findings highlight the sEMG coupling metrics' potential to reveal neuromuscular mechanisms that could aid the development of targeted rehabilitation strategies and help monitor DPN patients.
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Affiliation(s)
- Isabel Junquera-Godoy
- Centro de Investigación e Innovación en Bioingeniería (Ci2B), Universitat Politècnica de València (UPV), 46022 Valencia, Spain; (I.J.-G.); (G.G.-L.); (J.G.-T.); (J.S.); (G.P.-B.)
| | - José Luís Martinez-De-Juan
- Centro de Investigación e Innovación en Bioingeniería (Ci2B), Universitat Politècnica de València (UPV), 46022 Valencia, Spain; (I.J.-G.); (G.G.-L.); (J.G.-T.); (J.S.); (G.P.-B.)
| | - Gemma González-Lorente
- Centro de Investigación e Innovación en Bioingeniería (Ci2B), Universitat Politècnica de València (UPV), 46022 Valencia, Spain; (I.J.-G.); (G.G.-L.); (J.G.-T.); (J.S.); (G.P.-B.)
| | - José Miguel Carot-Sierra
- Departamento de Estadística e Investigación Operativa Aplicadas y Calidad, Universitat Politècnica de València (UPV), 46022 Valencia, Spain;
| | - Julio Gomis-Tena
- Centro de Investigación e Innovación en Bioingeniería (Ci2B), Universitat Politècnica de València (UPV), 46022 Valencia, Spain; (I.J.-G.); (G.G.-L.); (J.G.-T.); (J.S.); (G.P.-B.)
| | - Javier Saiz
- Centro de Investigación e Innovación en Bioingeniería (Ci2B), Universitat Politècnica de València (UPV), 46022 Valencia, Spain; (I.J.-G.); (G.G.-L.); (J.G.-T.); (J.S.); (G.P.-B.)
| | - Silvia García-Blasco
- Servicio de Rehabilitación, Departamento Salud Elche Hospital General de FISABIO, 03203 Elche, Spain; (S.G.-B.); (I.P.-M.)
| | - Isabel Pertusa-Mazón
- Servicio de Rehabilitación, Departamento Salud Elche Hospital General de FISABIO, 03203 Elche, Spain; (S.G.-B.); (I.P.-M.)
| | - Esther Soler-Climent
- Área de Investigación en Enfermería-Fisioterapia, Departamento Salud Elche Hospital General de FISABIO, 03203 Elche, Spain;
| | - Gema Prats-Boluda
- Centro de Investigación e Innovación en Bioingeniería (Ci2B), Universitat Politècnica de València (UPV), 46022 Valencia, Spain; (I.J.-G.); (G.G.-L.); (J.G.-T.); (J.S.); (G.P.-B.)
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Rajkumar S, Venkatraman V, Zidanyue Yang L, Parente B, Lee HJ, Lad SP. Healthcare Economics of High Frequency Spinal Cord Stimulation for Painful Diabetic Peripheral Neuropathy. J Diabetes Sci Technol 2024; 18:635-643. [PMID: 36314587 PMCID: PMC11089884 DOI: 10.1177/19322968221128321] [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] [Indexed: 11/07/2022]
Abstract
BACKGROUND Painful diabetic peripheral neuropathy (pDPN) is a debilitating complication of long-term diabetes. High-frequency spinal cord stimulation (HF-SCS) was recently shown to be an effective treatment option, but the associated healthcare resource utilization (HCRU) on real-world patient populations with pDPN is unknown. METHODS Using IBM MarketScan databases, we identified patients with HF-SCS implantation between January 2016 and December 2019 who had a diagnosis of diabetes or diabetic neuropathy within two years before implant. Cost data were collected for the six months before HF-SCS implantation (baseline) and for the periods of one, three, and six months post-implantation. The six-month explant rate was calculated. RESULTS A total of 132 patients met inclusion criteria. The median total cost at baseline was $19 220 and was $1356 at one month post-implant, $4858 at three months post-implant, and $13 305 at six months post-implant. The median baseline out-of-pocket cost was $1477 and was $710 at six months post-implant. The average total cost reduction from baseline to six months post-implant was $5118 (P < .001), or $853 per month. The median device acquisition cost was $35 755. The explant rate within six months was 2.1%. CONCLUSIONS High frequency spinal cord stimulation significantly reduces total HCRU in patients with pDPN, and based on the average monthly cost reduction of $853, we estimate that the therapy recoups acquisition costs within 3.5 years. As policy increasingly focuses on value-based care, it will be critical to consider the cost and outcomes of innovative therapies.
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Affiliation(s)
- Shashank Rajkumar
- Department of Neurosurgery, Duke University Hospital, Duke University Medical Center, Duke University School of Medicine, Durham, NC, USA
| | - Vishal Venkatraman
- Department of Neurosurgery, Duke University Hospital, Duke University Medical Center, Duke University School of Medicine, Durham, NC, USA
| | | | - Beth Parente
- Department of Neurosurgery, Duke University Hospital, Duke University Medical Center, Duke University School of Medicine, Durham, NC, USA
| | - Hui-Jie Lee
- Department of Biostatistics, Duke University, Durham, NC, USA
| | - Shivanand P. Lad
- Department of Neurosurgery, Duke University Hospital, Duke University Medical Center, Duke University School of Medicine, Durham, NC, USA
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Guo L, Pan Q, Cheng Z, Li Z, Jiang H, Zhang F, Li Y, Qiu W, Lu S, Tian J, Fu Y, Li F, Li D. Acetyllevocarnitine Hydrochloride for the Treatment of Diabetic Peripheral Neuropathy: A Phase 3 Randomized Clinical Trial in China. Diabetes 2024; 73:797-805. [PMID: 38320260 PMCID: PMC11043058 DOI: 10.2337/db23-0377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 02/01/2024] [Indexed: 02/08/2024]
Abstract
Diabetic peripheral neuropathy (DPN) is a highly prevalent chronic complication in type 2 diabetes (T2D) for which no effective treatment is available. In this multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial in China, patients with T2D with DPN received acetyllevocarnitine hydrochloride (ALC; 1,500 mg/day; n = 231) or placebo (n = 227) for 24 weeks, during which antidiabetic therapy was maintained. A significantly greater reduction in modified Toronto clinical neuropathy score (mTCNS) as the primary end point occurred in the ALC group (-6.9 ± 5.3 points) compared with the placebo group (-4.7 ± 5.2 points; P < 0.001). Effect sizes (ALC 1.31 and placebo 0.85) represented a 0.65-fold improvement in ALC treatment efficacy. The mTCNS values for pain did not differ significantly between the two groups (P = 0.066), whereas the remaining 10 components of mTCNS showed significant improvement in the ALC group compared with the placebo group (P < 0.05 for all). Overall results of electrophysiological measurements were inconclusive, with significant improvement in individual measurements limited primarily to the ulnar and median nerves. Incidence of treatment-emergent adverse events was 51.2% in the ALC group, among which urinary tract infection (5.9%) and hyperlipidemia (7.9%) were most frequent. ARTICLE HIGHLIGHTS
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Affiliation(s)
- Lixin Guo
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
| | - Qi Pan
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
| | - Zhifeng Cheng
- Department of Endocrinology, Fourth Hospital of Harbin Medical University, Harbin, China
| | - Zhiyong Li
- Department of Endocrinology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China
| | - Hongwei Jiang
- Department of Endocrinology, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
| | - Fang Zhang
- Department of Endocrinology, Kaifeng Hospital of Traditional Chinese Medicine, Kaifeng, China
| | - Yufeng Li
- Department of Endocrinology, Beijing Pinggu Hospital, Beijing, China
| | - Wei Qiu
- Department of Endocrinology, Xinxiang First People’s Hospital, Affiliated People’s Hospital of Xinxiang Medical University, Xinxiang, China
| | - Song Lu
- Department of Endocrinology, Chongqing General Hospital, Chongqing, China
| | - Junhang Tian
- Department of Endocrinology, Luoyang Third People’s Hospital, Luoyang, China
| | - Yanqin Fu
- Department of Endocrinology, Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Fangqiong Li
- Haisco Pharmaceutical Group Co., Ltd., Chengdu, China
| | - Danqing Li
- Haisco Pharmaceutical Group Co., Ltd., Chengdu, China
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11
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Alshowair A, Altamimi S, Alruhaimi FA, Alshahrani S, Alsuwailem F, Alkhaldi M, Abdalla H, Alkhuraiji FH, Alaqeel MS, Almureef SS, Alhawasy S, Abdel-Azeem A. Cost-Savings Associated with Multi-Disciplinary Team Approach for Reducing Macrovascular and Microvascular Complications in Patients with Type 2 Diabetes: A Predictive Model. CLINICOECONOMICS AND OUTCOMES RESEARCH 2024; 16:211-223. [PMID: 38596283 PMCID: PMC11001564 DOI: 10.2147/ceor.s451739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Accepted: 03/26/2024] [Indexed: 04/11/2024] Open
Abstract
Purpose This study aims to predict the expected cost savings associated with implementing a multidisciplinary team (MDT) approach to reduce macrovascular and microvascular complications among patients with type 2 diabetes mellitus (T2DM). Methods This economic evaluation study was conducted in Riyadh First Health Cluster, Saudi Arabia as a predictive model conceptualized by the authors based on models used in previous studies, particularly the CORE Diabetes Model. Our model was designed based on 1) the level of glycemic control among 24,755 T2DM patients served by MDTs; 2) the expected incidence of diabetes-related complications without intervention; 3) the predicted risk reduction of developing diabetes-related complications with MDTs. Costs of complications and cost savings were then calculated and expressed as mean incremental annual cost savings adjusted for a 1% reduction in HbA1c, and a 10 mmHg reduction in systolic blood pressure (SBP). Results Along with the expected reduction in all diabetes-related complications, the average incremental cost savings per diabetic patient is predicted to be ($38,878) with approximately ($11,108) in the year of complication onset and ($27,770) over the subsequent post-index 10-years. On adjustment of cost savings, the average incremental cost savings are predicted to be ($22,869) for each 1% reduction in HbA1c per diabetic patient and ($27,770) for every 10 mmHg reduction in SBP per diabetic patient. Conclusion MDT as a model of care is effective in glycemic control among T2DM patients with a predicted significant reduction of all diabetes-related complications and in turn, a predicted significant cost savings.
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Affiliation(s)
- Abdulmajeed Alshowair
- Community Health Excellence, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia
| | - Saleh Altamimi
- Community Health Excellence, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia
| | - Faisal A Alruhaimi
- Community Health Excellence, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia
| | - Saad Alshahrani
- Academic and Training Affairs, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia
| | - Fatima Alsuwailem
- Population Health Management and Research, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia
| | - Mona Alkhaldi
- Health Administration Office, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia
| | - Haiam Abdalla
- Model of Care, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia
| | | | - Montaser Saad Alaqeel
- Financial Affairs, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia
| | | | - Salman Alhawasy
- Reporting Department, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia
| | - Amro Abdel-Azeem
- Population Health Management and Research, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia
- Department of Community, Environmental and Occupational Medicine, Faculty of Medicine Zagazig University, Zagazig, Egypt
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12
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Mallick-Searle T, Adler JA. Update on Treating Painful Diabetic Peripheral Neuropathy: A Review of Current US Guidelines with a Focus on the Most Recently Approved Management Options. J Pain Res 2024; 17:1005-1028. [PMID: 38505500 PMCID: PMC10949339 DOI: 10.2147/jpr.s442595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Accepted: 02/26/2024] [Indexed: 03/21/2024] Open
Abstract
Painful diabetic peripheral neuropathy (DPN) is a highly prevalent and disabling complication of diabetes that is often misdiagnosed and undertreated. The management of painful DPN involves treating its underlying cause via lifestyle modifications and intensive glucose control, targeting its pathogenesis, and providing symptomatic pain relief, thereby improving patient function and health-related quality of life. Four pharmacologic options are currently approved by the US Food and Drug Administration (FDA) to treat painful DPN. These include three oral medications (duloxetine, pregabalin, and tapentadol extended release) and one topical agent (capsaicin 8% topical system). More recently, the FDA approved several spinal cord stimulation (SCS) devices to treat refractory painful DPN. Although not FDA-approved specifically to treat painful DPN, tricyclic antidepressants, serotonin/norepinephrine reuptake inhibitors, gabapentinoids, and sodium channel blockers are common first-line oral options in clinical practice. Other strategies may be used as part of individualized comprehensive pain management plans. This article provides an overview of the most recent US guidelines for managing painful DPN, with a focus on the two most recently approved treatment options (SCS and capsaicin 8% topical system), as well as evidence for using FDA-approved and guideline-supported drugs and devices. Also discussed are unmet needs for this patient population, and evidence for potential future treatments for painful DPN, including drugs with novel mechanisms of action, electrical stimulation devices, and nutraceuticals.
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13
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Ma K, Cheng Z, Jiang H, Lin Z, Liu C, Liu X, Lu L, Lu Y, Tao W, Wang S, Yang X, Yi Q, Zhang X, Zhang Y, Liu Y. Expert Consensus on Ion Channel Drugs for Chronic Pain Treatment in China. J Pain Res 2024; 17:953-963. [PMID: 38476873 PMCID: PMC10929561 DOI: 10.2147/jpr.s445171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 01/22/2024] [Indexed: 03/14/2024] Open
Abstract
Ion channel drugs have been increasing used for chronic pain management with progress in the development of selective calcium channel modulators. Although ion channel drugs have been proven safe and effective in clinical practice, uncertainty remains regarding its use to treat chronic pain. To standardize the clinical practice of ion channel drug for the treatment of chronic pain, the National Health Commission Capacity Building and Continuing Education Center for Pain Diagnosis and Treatment Special Ability Training Project established an expert group to form an expert consensus on the use of ion channel drugs for the treatment of chronic pain after repeated discussions on existing medical evidence combined with the well clinical experience of experts. The consensus provided information on the mechanism of action of ion channel drugs and their recommendations, caution use, contraindications, and precautions for their use in special populations to support doctors in their clinical decision-making.
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Affiliation(s)
- Ke Ma
- Department of Algology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Zhixiang Cheng
- Department of Algology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Hao Jiang
- Department of Algology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Zhangya Lin
- Department of Neurosurgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Chuansheng Liu
- Department of Algology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China
| | - Xianguo Liu
- Pain Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Lijuan Lu
- Department of Pain Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China
| | - Yan Lu
- Department of Algology, Xijing Hospital, The Fourth Military Medical University, Xian, People’s Republic of China
| | - Wei Tao
- Department of Neurosurgery, Shenzhen University General Hospital, Shenzhen, People’s Republic of China
| | - Suoliang Wang
- Department of Algology, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Xiaoqiu Yang
- Department of Algology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Qishan Yi
- Department of Algology, The Yibin First People’s Hospital Affiliated Chongqing Medical University, Yibin, People’s Republic of China
| | - Xiaomei Zhang
- Department of Algology, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China
| | - Ying Zhang
- Department of Algology. Hospital (T.C.M) Affiliated to Southwest Medical University, Luzhou, People’s Republic of China
| | - Yanqing Liu
- Department of Algology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China
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14
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Li S, Zheng Y, Kang Y, He X, Zheng Y, Jiang M, Xu X, Ma L, Wang X, Zhang K, Shao X, Fang J, Jiang Y. Electroacupuncture alleviates streptozotocin-induced diabetic neuropathic pain via suppressing phosphorylated CaMKIIα in rats. Neuroreport 2024; 35:258-268. [PMID: 38305135 PMCID: PMC10852042 DOI: 10.1097/wnr.0000000000002000] [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: 12/09/2023] [Accepted: 01/02/2024] [Indexed: 02/03/2024]
Abstract
Diabetic neuropathic pain (DNP) is a frequent complication of diabetes. Calcium/calmodulin-dependent protein kinase II α (CaMKIIα), a multi-functional serine/threonine kinase subunit, is mainly located in the surface layer of the spinal cord dorsal horn (SCDH) and the primary sensory neurons in dorsal root ganglion (DRG). Numerous studies have indicated electroacupuncture (EA) takes effect in various kinds of pain. In this research, we explored whether CaMKIIα on rats' SCDH and DRG participated in DNP and further explored the mechanisms underlying the analgesic effects of EA. The DNP model in rats was successfully established by intraperitoneal injection of streptozotocin. Certain DNP rats were treated with intrathecal injections of KN93, a CaMKII antagonist, and some of the DNP rats received EA intervention. The general conditions, behaviors, the expressions of CaMKIIα and phosphorylated CaMKIIα (p-CaMKIIα) were evaluated. DNP rats' paw withdrawal threshold was reduced and the expressions of p-CaMKIIα in SCDH and DRG were upregulated compared with the Normal group, while the level of CaMKIIα showed no significance. KN93 attenuated DNP rats' hyperalgesia and reduced the expressions of p-CaMKIIα. We also found EA attenuated the hyperalgesia of DNP rats and reduced the expressions of p-CaMKIIα. The above findings suggest that p-CaMKIIα in SCDH and DRG is involved in DNP. The analgesic effect of EA in DNP might be related to the downregulation of p-CaMKIIα expression level. Our study further supports that EA can be an effective clinical treatment for DNP.
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Affiliation(s)
- Siyi Li
- Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
| | - Yinmu Zheng
- Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
| | - Yurong Kang
- Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
| | - Xiaofen He
- Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
| | - Yu Zheng
- Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
| | - Minjian Jiang
- Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
| | - Xinnan Xu
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
| | - Liqian Ma
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
| | - Xiaoxiang Wang
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
| | - Kunlong Zhang
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
| | - Xiaomei Shao
- Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
| | - Jianqiao Fang
- Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
| | - Yongliang Jiang
- Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
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15
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Zhao B, Zhang Q, He Y, Cao W, Song W, Liang X. Targeted metabolomics reveals the aberrant energy status in diabetic peripheral neuropathy and the neuroprotective mechanism of traditional Chinese medicine JinMaiTong. J Pharm Anal 2024; 14:225-243. [PMID: 38464790 PMCID: PMC10921333 DOI: 10.1016/j.jpha.2023.09.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 08/15/2023] [Accepted: 09/18/2023] [Indexed: 03/12/2024] Open
Abstract
Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However, the integrated profile of energy metabolism, especially the central carbohydrate metabolism, remains unclear in DPN. Here, we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats. Furthermore, JinMaiTong (JMT), a traditional Chinese medicine (TCM) formula, was found to be effective for DPN, improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration. JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions, including excessive glycolysis restoration, tricarboxylic acid cycle improvement, and increased adenosine triphosphate (ATP) generation. Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions, which was remarkably corrected by JMT treatment. In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Our results expand the therapeutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs, such as JMT, as an effective strategy for its treatment.
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Affiliation(s)
- Bingjia Zhao
- Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Qian Zhang
- Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Yiqian He
- Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Weifang Cao
- Institute of Basic Medicine Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China
| | - Wei Song
- Medical Research Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Xiaochun Liang
- Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China
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16
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Elliott J, Sloan G, Stevens L, Selvarajah D, Cruccu G, Gandhi RA, Kempler P, Fuller JH, Chaturvedi N, Tesfaye S. Female sex is a risk factor for painful diabetic peripheral neuropathy: the EURODIAB prospective diabetes complications study. Diabetologia 2024; 67:190-198. [PMID: 37870649 PMCID: PMC10709240 DOI: 10.1007/s00125-023-06025-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 09/05/2023] [Indexed: 10/24/2023]
Abstract
AIMS/HYPOTHESIS While the risk factors for diabetic peripheral neuropathy (DPN) are now well recognised, the risk factors for painful DPN remain unknown. We performed analysis of the EURODIAB Prospective Complications Study data to elucidate the incidence and risk factors of painful DPN. METHODS The EURODIAB Prospective Complications Study recruited 3250 participants with type 1 diabetes who were followed up for 7.3±0.6 (mean ± SD) years. To evaluate DPN, a standardised protocol was used, including clinical assessment, quantitative sensory testing and autonomic function tests. Painful DPN (defined as painful neuropathic symptoms in the legs in participants with confirmed DPN) was assessed at baseline and follow-up. RESULTS At baseline, 234 (25.2%) out of 927 participants with DPN had painful DPN. At follow-up, incident DPN developed in 276 (23.5%) of 1172 participants. Of these, 41 (14.9%) had incident painful DPN. Most of the participants who developed incident painful DPN were female (73% vs 48% painless DPN p=0.003) and this remained significant after adjustment for duration of diabetes and HbA1c (OR 2.69 [95% CI 1.41, 6.23], p=0.004). The proportion of participants with macro- or microalbuminuria was lower in those with painful DPN compared with painless DPN (15% vs 34%, p=0.02), and this association remained after adjusting for HbA1c, diabetes duration and sex (p=0.03). CONCLUSIONS/INTERPRETATION In this first prospective study to investigate the risk factors for painful DPN, we definitively demonstrate that female sex is a risk factor for painful DPN. Additionally, there is less evidence of diabetic nephropathy in incident painful, compared with painless, DPN. Thus, painful DPN is not driven by cardiometabolic factors traditionally associated with microvascular disease. Sex differences may therefore play an important role in the pathophysiology of neuropathic pain in diabetes. Future studies need to look at psychosocial, genetic and other factors in the development of painful DPN.
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Affiliation(s)
- Jackie Elliott
- Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield, UK
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
| | - Gordon Sloan
- Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield, UK
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
| | - Lynda Stevens
- Department of Epidemiology and Public Health, University College, London, UK
| | - Dinesh Selvarajah
- Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield, UK
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
| | - Giorgio Cruccu
- Department of Neurological Sciences, La Sapienza University, Rome, Italy
| | - Rajiv A Gandhi
- Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield, UK
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
| | - Peter Kempler
- First Department of Medicine, Semmelweis University, Budapest, Hungary
| | - John H Fuller
- Epidemiology and Public Health, Imperial College of Science, Technology & Medicine, London, UK
| | - Nishi Chaturvedi
- MRC Unit for Lifelong Health & Ageing at UCL, Institute of Cardiovascular Sciences, University College London, London, UK
| | - Solomon Tesfaye
- Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield, UK.
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
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17
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Medeiros Dantas J, de Jesus Oliveira M, Silva LAO, Batista S, Dagostin CS, Schachter DC. Monotherapy Versus Combination Therapy in the Treatment of Painful Diabetic Neuropathy: A Systematic Review and Meta-analysis. Clin Drug Investig 2023; 43:905-914. [PMID: 37940831 DOI: 10.1007/s40261-023-01318-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/12/2023] [Indexed: 11/10/2023]
Abstract
BACKGROUND AND OBJECTIVE Painful peripheral neuropathy is a common and challenging complication of diabetes mellitus. Combination therapy is used widely by clinicians, although strong evidence for efficacy and safety is lacking. The goal of this study is to compare the efficacy and safety of combination versus monotherapy of first-line medications for peripheral diabetic neuropathy. METHODS PubMed, Embase, Cochrane Central, and clinicaltrials.gov databases were searched on December 5, 2022, for randomized clinical trials comparing combined therapy with gabapentinoids and either tricyclic antidepressants (TCAs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) versus monotherapy with any of these drugs. Pooled mean differences (MD) with a 95% confidence interval (CI) were computed for pain outcomes, measured on an 11-point numeric rating scale averaging pain scores in the last 7 days. Risk ratios (RRs) were computed for binary endpoints. Risk assessment was performed using the Risk of Bias 2 tool. RESULTS A total of five randomized studies and 916 patients were included. Follow-up ranged from 6 to 12 weeks. Mean pain reduction was greater for combination therapy than monotherapy (MD - 0.39; 95% CI - 0.67 to - 0.12; p = 0.005). Similarly, there was an improvement in ≥ 30% reduction in average pain (RR 1.16; 95% CI 1.07-1.26; p < 0.01) with combination therapy. In contrast, there was no significant difference between groups in ≥ 50% reduction in average pain (RR 1.21; 95% CI 0.99-1.49; p = 0.06). When comparing combination therapy versus gabapentinoid monotherapy, there was also a significant reduction in average pain (MD - 0.61; 95% CI - 0.85 to - 0.37; p < 0.01) with combination therapy. CONCLUSION In patients with painful diabetic peripheral neuropathy, the combination of gabapentinoids with TCAs or SNRIs is associated with a greater reduction in pain as compared with monotherapy, although this difference may not translate into a clinically important difference.
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Affiliation(s)
- Julyana Medeiros Dantas
- Department of Clinical Medicine, Universidade Federal do Rio Grande do Norte, Avenida Nilo Peçanha, 620 - Petrópolis, Natal, RN, Brazil.
| | | | | | - Sávio Batista
- Department of Clinical Medicine, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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18
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Petersen EA. Spinal cord stimulation in painful diabetic neuropathy: An overview. Diabetes Res Clin Pract 2023; 206 Suppl 1:110760. [PMID: 38245324 DOI: 10.1016/j.diabres.2023.110760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 05/30/2023] [Indexed: 01/22/2024]
Abstract
Up to 25% of people with diabetes develop painful diabetic neuropathy (PDN). The standard of care pharmacotherapies for PDN have limited efficacy with a considerable side effect profile. Spinal cord stimulation (SCS) is a form of electrical neurostimulation that modulates neural function via electrodes implanted into the spinal epidural space. While low frequency SCS has been shown to be potentially effective for treating pain associated with neuropathies, it masks pain perception by inducing paresthesia. Compared to low frequency SCS, high frequency (10 kHz) SCS delivers paresthesia-free therapy. As was shown in a randomized controlled trial, SENZA-PDN (NCT03228420), 10 kHz SCS is safe and effective for the treatment of painful diabetic neuropathy. 10 kHz SCS offered a comprehensive treatment that improved pain levels, sleep, quality of life, and neurological function. These improvements correlated with a high degree of patient satisfaction. 10 kHz SCS provides a safe, durable and effective treatment for PDN with the unique potential to improve neurological function. In patients for whom durable, effective treatments have been limited thus far, the findings of the SENZA-PDN study are encouraging.
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Affiliation(s)
- Erika A Petersen
- University of Arkansas for Medical Sciences, Little Rock, AR, USA.
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19
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Zhang F, Yu Y, Yin S, Hu G, Yang X, Tong K, Yu R. Is acupoint injection the optimal way to administer mecobalamin for diabetic peripheral neuropathy? A meta-analysis and trial sequential analysis. Front Neurol 2023; 14:1186420. [PMID: 37920836 PMCID: PMC10619916 DOI: 10.3389/fneur.2023.1186420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 09/07/2023] [Indexed: 11/04/2023] Open
Abstract
Objective Mecobalamin is a commonly used drug in the treatment of diabetic peripheral neuropathy (DPN). This study aimed to systematically evaluate the efficacy and safety of acupoint injection of mecobalamin for DPN. Methods Relevant clinical trials on acupoint injection of mecobalamin for DPN published before 31 January 2023 were searched in eight commonly used databases. After screening and confirming the included studies, meta-analysis and trial sequential analysis were performed. Results A total of 10 relevant studies were confirmed, and the total sample size was 927 cases. On the efficacy endpoints, meta-analysis showed that compared with other administration methods, acupoint injection of mecobalamin significantly increased the clinical effective rate by 27% [RR = 1.27, 95% CI = (1.19, 1.36), P < 0.00001], motor nerve conduction velocity (median nerve) by 5.93 m/s [MD = 5.93, 95% CI = (4.79, 7.07), P < 0.00001], motor nerve conduction velocity (common peroneal nerve) by 5.66 m/s [MD = 5.66, 95% CI = (2.89, 8.43), P < 0.0001], sensory nerve conduction velocity (median nerve) by 4.83 m/s [MD = 4.83, 95% CI = (3.75, 5.90), P < 0.00001], and sensory nerve conduction velocity (common peroneal nerve) by 3.60 m/s [MD = 3.60, 95% CI = (2.49, 4.71), P < 0.00001], and trial sequential analysis showed these benefits were conclusive. In terms of safety endpoints, meta-analysis indicated that the total adverse events for acupoint injection were comparable to other methods of administration, and trial sequential analysis suggested that the results needed to be validated by more studies. Subgroup analysis demonstrated that the benefits of acupoint injections of mecobalamin were not limited by the dose, duration of treatment, or number of acupoints reported in the included studies. Harbord's test showed no significant publication bias (P = 0.106). Conclusion The efficacy of acupoint injection of mecobalamin for DPN was significantly better than other administrations, and its safety was comparable to other administrations. Therefore, acupoint injection may be the optimal method of mecobalamin for DPN. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=454120, identifier: CRD42023454120.
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Affiliation(s)
- Fei Zhang
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Yunfeng Yu
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
- The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Shuang Yin
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Gang Hu
- The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Xinyu Yang
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Keke Tong
- The Hospital of Hunan University of Traditional Chinese Medicine, Changde, Hunan, China
| | - Rong Yu
- The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
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Hassanzadeh S, Bagheri S, Majid Ahmadi S, Ahmadi SA, Moradishibany I, Dolatkhah H, Reisi S. Effectiveness of oral clonidine and gabapentin on peripheral neuropathy in diabetic patients in southwestern Iran: a randomized clinical trial. BMC Endocr Disord 2023; 23:224. [PMID: 37845651 PMCID: PMC10577942 DOI: 10.1186/s12902-023-01486-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 10/11/2023] [Indexed: 10/18/2023] Open
Abstract
BACKGROUND Peripheral neuropathy is not only the most prevalent consequence of diabetes but also the main reason for foot ulceration, disability, and amputation. Therefore, the current study aims to determine the effectiveness of oral clonidine and gabapentin on peripheral neuropathy in diabetic patients. METHODS This 12-week, randomized, and parallel-group trial was conducted to compare the efficacy of oral clonidine and gabapentin with gabapentin alone in diabetic patients in southwest Iran during the first half of 2021. Thirty patients with type 2 diabetes with peripheral neuropathy as assessed by a visual analog scale (VAS) and divided into two groups of 15 patients, treated for up to three months. The data were analyzed using SPSS-21 software. In order to report the results, descriptive indices, independent t-test, one-way analysis of covariance (ANCOVA) and analysis of variance with repeated measures were used. RESULTS The mean and standard deviation of the age of the participants in the clonidine + gabapentin group was equal to 50.20 ± 7.44, and in the gabapentin group was equal to 50.47 ± 7.57 (t = 0.10, P-value = 0.923). This research showed a significant difference between the clonidine + gabapentin group and with gabapentin group in terms of neuropathic pain and the severity of neuropathic pain (P < 0.001). CONCLUSIONS According to this research results, clonidine + gabapentin can reduce neuropathic pain and the severity of neuropathic pain in diabetic patients. Therefore, it is recommended that healthcare professionals with diabetes expertise prescribe these medications to reduce neuropathic pain and its severity. TRIAL REGISTRATION This study was registered in the Iranian Clinical Trials System with the ID (IRCT20211106052983N1) on 14/01/2022.
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Affiliation(s)
- Sajad Hassanzadeh
- Department of Internal Medicine, School of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Soraya Bagheri
- Department of Internal Medicine, School of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Seyed Majid Ahmadi
- Department of Internal Medicine, School of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran.
| | | | - Isaac Moradishibany
- Department of Internal Medicine, School of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Hosein Dolatkhah
- Department of Internal Medicine, School of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Sajjad Reisi
- Genetic and Environmental Adventures Research Center, School of Abarkouh Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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21
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Taylor RS, Lad SP, White JL, Stauss TG, Healey BE, Sacks NC, McLin R, Patil S, Jaasma MJ, Caraway DL, Petersen EA. Health care resource utilization and costs in patients with painful diabetic neuropathy treated with 10 kHz spinal cord stimulation therapy. J Manag Care Spec Pharm 2023; 29:1021-1029. [PMID: 37610114 PMCID: PMC10508838 DOI: 10.18553/jmcp.2023.29.9.1021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/24/2023]
Abstract
BACKGROUND: Diabetic peripheral neuropathy, a common comorbidity of diabetes, is a neurodegenerative disorder that targets sensory, autonomic, and motor nerves frequently associated with painful diabetic neuropathy (PDN). PDN carries an economic burden as the result of reduced work and productivity. A recent multicenter randomized controlled trial, SENZA-PDN (NCT03228420), assessed the impact of high-frequency (10 kHz) spinal cord stimulation (SCS) on pain relief. The effects of high-frequency SCS on health care resource utilization and medical costs are not known. OBJECTIVE: To evaluate the effect of high-frequency (10 kHz) SCS on health care resource utilization (HRU) and medical costs in patients with PDN using data from the SENZA-PDN trial. METHODS: Participants with PDN were randomly assigned 1:1 to receive either 10 kHz SCS plus conventional medical management (CMM) (SCS treatment group) or CMM alone (CMM treatment group). Patient outcomes and HRU up to the 6-month follow-up are reported here. Costs (2020 USD) for each service was estimated based on publicly available Medicare fee schedules, Medicare claims data, and literature. HRU metrics of inpatient and outpatient contacts and costs are reported as means and SDs. Univariate and bivariate analyses were used to compare SCS and CMM treatment groups at 6 months. RESULTS: At 6-month follow up, the SCS arm experienced approximately half the mean rate of hospitalizations per patient compared with the CMM treatment group (0.08 vs 0.15; P = 0.066). The CMM treatment group's total health care costs per patient were approximately 51% higher compared with the SCS treatment group (equivalent to mean annual cost per patient of $9,532 vs $6,300). CONCLUSIONS: Our analysis of the SENZA-PDN trial indicates that the addition of 10 kHz SCS therapy results in lower rates of hospitalization and consequently lower health care costs among patients with PDN compared with those receiving conventional management alone.
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Affiliation(s)
- Rod S. Taylor
- MRC/CSO Social and Public Health Sciences Unit, Robertson Centre for Biostatistics, School of Health & Wellbeing, University of Glasgow, UK
| | | | | | | | | | - Naomi C. Sacks
- PRECISIONheor, Boston, MA
- EpidStrategies, A Division of ToxStrategies, LLC, Boston, MA
| | - Ronaé McLin
- PRECISIONheor, New York, NY, now with Case Western Reserve University School of Medicine, Cleveland, OH
| | | | | | | | - Erika A. Petersen
- Department of Neurosurgery, University of Arkansas for Medical Sciences, Little Rock, AR
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22
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Lin Q, Li K, Chen Y, Xie J, Wu C, Cui C, Deng B. Oxidative Stress in Diabetic Peripheral Neuropathy: Pathway and Mechanism-Based Treatment. Mol Neurobiol 2023:10.1007/s12035-023-03342-7. [PMID: 37115404 DOI: 10.1007/s12035-023-03342-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 04/04/2023] [Indexed: 04/29/2023]
Abstract
Diabetic peripheral neuropathy (DPN) is a major complication of diabetes mellitus with a high incidence. Oxidative stress, which is a crucial pathophysiological pathway of DPN, has attracted much attention. The distortion in the redox balance due to the overproduction of reactive oxygen species (ROS) and the deregulation of antioxidant defense systems promotes oxidative damage in DPN. Therefore, we have focused on the role of oxidative stress in the pathogenesis of DPN and elucidated its interaction with other physiological pathways, such as the glycolytic pathway, polyol pathway, advanced glycosylation end products, protein kinase C pathway, inflammation, and non-coding RNAs. These interactions provide novel therapeutic options targeting oxidative stress for DPN. Furthermore, our review addresses the latest therapeutic strategies targeting oxidative stress for the rehabilitation of DPN. Antioxidant supplements and exercise have been proposed as fundamental therapeutic strategies for diabetic patients through ROS-mediated mechanisms. In addition, several novel drug delivery systems can improve the bioavailability of antioxidants and the efficacy of DPN.
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Affiliation(s)
- Qingxia Lin
- Department of Psychiatry, First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Kezheng Li
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
- First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Yinuo Chen
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
- First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Jiali Xie
- Department of Neurology, Shanghai East Hospital, Tongji University, Shanghai, People's Republic of China
| | - Chunxue Wu
- Department of Neurology, Wencheng County People's Hospital, Wenzhou, People's Republic of China
| | - Can Cui
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Binbin Deng
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.
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23
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Liu X, Chen D, Fu H, Liu X, Zhang Q, Zhang J, Ding M, Wen J, Chang B. Development and validation of a risk prediction model for early diabetic peripheral neuropathy based on a systematic review and meta-analysis. Front Public Health 2023; 11:1128069. [PMID: 36908480 PMCID: PMC9992641 DOI: 10.3389/fpubh.2023.1128069] [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: 12/20/2022] [Accepted: 02/06/2023] [Indexed: 02/24/2023] Open
Abstract
Background Early identification and intervention of diabetic peripheral neuropathy is beneficial to improve clinical outcome. Objective To establish a risk prediction model for diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM). Methods The derivation cohort was from a meta-analysis. Risk factors and the corresponding risk ratio (RR) were extracted. Only risk factors with statistical significance were included in the model and were scored by their weightings. An external cohort were used to validate this model. The outcome was the occurrence of DPN. Results A total of 95,604 patients with T2DM from 18 cohorts were included. Age, smoking, body mass index, duration of diabetes, hemoglobin A1c, low HDL-c, high triglyceride, hypertension, diabetic retinopathy, diabetic kidney disease, and cardiovascular disease were enrolled in the final model. The highest score was 52.0. The median follow-up of validation cohort was 4.29 years. The optimal cut-off point was 17.0, with a sensitivity of 0.846 and a specificity of 0.668, respectively. According to the total scores, patients from the validation cohort were divided into low-, moderate-, high- and very high-risk groups. The risk of developing DPN was significantly increased in moderate- (RR 3.3, 95% CI 1.5-7.2, P = 0.020), high- (RR 15.5, 95% CI 7.6-31.6, P < 0.001), and very high-risk groups (RR 45.0, 95% CI 20.5-98.8, P < 0.001) compared with the low-risk group. Conclusion A risk prediction model for DPN including 11 common clinical indicators were established. It is a simple and reliable tool for early prevention and intervention of DPN in patients with T2DM.
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Affiliation(s)
- Xixi Liu
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Dong Chen
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Hongmin Fu
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Xinbang Liu
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Qiumei Zhang
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Jingyun Zhang
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Min Ding
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Juanjuan Wen
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Bai Chang
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
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24
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Dludla PV, Nkambule BB, Cirilli I, Marcheggiani F, Mabhida SE, Ziqubu K, Ntamo Y, Jack B, Nyambuya TM, Hanser S, Mazibuko-Mbeje SE. Capsaicin, its clinical significance in patients with painful diabetic neuropathy. Biomed Pharmacother 2022; 153:113439. [DOI: 10.1016/j.biopha.2022.113439] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 07/14/2022] [Accepted: 07/15/2022] [Indexed: 12/14/2022] Open
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25
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Tesfaye S, Sloan G, Petrie J, White D, Bradburn M, Julious S, Rajbhandari S, Sharma S, Rayman G, Gouni R, Alam U, Cooper C, Loban A, Sutherland K, Glover R, Waterhouse S, Turton E, Horspool M, Gandhi R, Maguire D, Jude EB, Ahmed SH, Vas P, Hariman C, McDougall C, Devers M, Tsatlidis V, Johnson M, Rice ASC, Bouhassira D, Bennett DL, Selvarajah D. Comparison of amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine supplemented with pregabalin for the treatment of diabetic peripheral neuropathic pain (OPTION-DM): a multicentre, double-blind, randomised crossover trial. Lancet 2022; 400:680-690. [PMID: 36007534 PMCID: PMC9418415 DOI: 10.1016/s0140-6736(22)01472-6] [Citation(s) in RCA: 89] [Impact Index Per Article: 29.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 07/13/2022] [Accepted: 07/28/2022] [Indexed: 10/25/2022]
Abstract
BACKGROUND Diabetic peripheral neuropathic pain (DPNP) is common and often distressing. Most guidelines recommend amitriptyline, duloxetine, pregabalin, or gabapentin as initial analgesic treatment for DPNP, but there is little comparative evidence on which one is best or whether they should be combined. We aimed to assess the efficacy and tolerability of different combinations of first-line drugs for treatment of DPNP. METHODS OPTION-DM was a multicentre, randomised, double-blind, crossover trial in patients with DPNP with mean daily pain numerical rating scale (NRS) of 4 or higher (scale is 0-10) from 13 UK centres. Participants were randomly assigned (1:1:1:1:1:1), with a predetermined randomisation schedule stratified by site using permuted blocks of size six or 12, to receive one of six ordered sequences of the three treatment pathways: amitriptyline supplemented with pregabalin (A-P), pregabalin supplemented with amitriptyline (P-A), and duloxetine supplemented with pregabalin (D-P), each pathway lasting 16 weeks. Monotherapy was given for 6 weeks and was supplemented with the combination medication if there was suboptimal pain relief (NRS >3), reflecting current clinical practice. Both treatments were titrated towards maximum tolerated dose (75 mg per day for amitriptyline, 120 mg per day for duloxetine, and 600 mg per day for pregabalin). The primary outcome was the difference in 7-day average daily pain during the final week of each pathway. This trial is registered with ISRCTN, ISRCTN17545443. FINDINGS Between Nov 14, 2017, and July 29, 2019, 252 patients were screened, 140 patients were randomly assigned, and 130 started a treatment pathway (with 84 completing at least two pathways) and were analysed for the primary outcome. The 7-day average NRS scores at week 16 decreased from a mean 6·6 (SD 1·5) at baseline to 3·3 (1·8) at week 16 in all three pathways. The mean difference was -0·1 (98·3% CI -0·5 to 0·3) for D-P versus A-P, -0·1 (-0·5 to 0·3) for P-A versus A-P, and 0·0 (-0·4 to 0·4) for P-A versus D-P, and thus not significant. Mean NRS reduction in patients on combination therapy was greater than in those who remained on monotherapy (1·0 [SD 1·3] vs 0·2 [1·5]). Adverse events were predictable for the monotherapies: we observed a significant increase in dizziness in the P-A pathway, nausea in the D-P pathway, and dry mouth in the A-P pathway. INTERPRETATION To our knowledge, this was the largest and longest ever, head-to-head, crossover neuropathic pain trial. We showed that all three treatment pathways and monotherapies had similar analgesic efficacy. Combination treatment was well tolerated and led to improved pain relief in patients with suboptimal pain control with a monotherapy. FUNDING National Institute for Health Research (NIHR) Health Technology Assessment programme.
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Affiliation(s)
- Solomon Tesfaye
- Diabetes Research Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK; School of Health and Related Research, and Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
| | - Gordon Sloan
- Diabetes Research Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Jennifer Petrie
- Clinical Trials Research Unit, University of Sheffield, Sheffield, UK
| | - David White
- Clinical Trials Research Unit, University of Sheffield, Sheffield, UK
| | - Mike Bradburn
- Clinical Trials Research Unit, University of Sheffield, Sheffield, UK
| | - Stephen Julious
- Medical Statistics Group, University of Sheffield, Sheffield, UK
| | - Satyan Rajbhandari
- Department of Diabetes, Lancashire Teaching Hospitals NHS Trust, Chorley, UK
| | - Sanjeev Sharma
- Diabetes and Endocrine Centre, East Suffolk and North Essex NHS Foundation Trust, Ipswich, UK
| | - Gerry Rayman
- Diabetes and Endocrine Centre, East Suffolk and North Essex NHS Foundation Trust, Ipswich, UK
| | - Ravikanth Gouni
- Diabetes and Endocrine Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Uazman Alam
- Department of Cardiovascular & Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK; Liverpool University Hospital NHS Foundation Trust, Liverpool, UK
| | - Cindy Cooper
- Clinical Trials Research Unit, University of Sheffield, Sheffield, UK
| | - Amanda Loban
- Clinical Trials Research Unit, University of Sheffield, Sheffield, UK
| | - Katie Sutherland
- Clinical Trials Research Unit, University of Sheffield, Sheffield, UK
| | - Rachel Glover
- Clinical Trials Research Unit, University of Sheffield, Sheffield, UK
| | - Simon Waterhouse
- Clinical Trials Research Unit, University of Sheffield, Sheffield, UK
| | - Emily Turton
- Clinical Trials Research Unit, University of Sheffield, Sheffield, UK
| | | | - Rajiv Gandhi
- Diabetes Research Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Deirdre Maguire
- Department of Diabetes and Endocrinology, Harrogate and District NHS Foundation Trust, Harrogate, UK
| | - Edward B Jude
- Department of Diabetes and Endocrinology, Tameside and Glossop Integrated Care NHS Foundation Trust, Ashton under Lyne, UK; Division of Diabetes, Endocrinology & Gastroenterology, University of Manchester, Manchester, UK
| | - Syed H Ahmed
- School of Medicine, University of Liverpool, Liverpool, UK; Department of Diabetes and Endocrinology, Countess of Chester Hospital NHS Foundation Trust, Chester, UK
| | - Prashanth Vas
- Department of Diabetes, King's College Hospital NHS Foundation Trust, London, UK
| | - Christian Hariman
- Department of Diabetes and Endocrinology, The Royal Wolverhampton NHS Trust, Wolverhampton, UK
| | - Claire McDougall
- Department of Medicine, University Hospital Hairmyres, NHS Lanarkshire, Hairmyres, UK
| | - Marion Devers
- Department of Diabetes, University Hospital Monklands, NHS Lanarkshire, Monklands, UK
| | - Vasileios Tsatlidis
- Department of Endocrinology and Diabetes, Gateshead Health NHS Foundation Trust, Gateshead, UK
| | | | - Andrew S C Rice
- Pain Research, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK
| | | | - David L Bennett
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
| | - Dinesh Selvarajah
- School of Health and Related Research, and Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
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Tarçın G, Ercan O. Emergence of Ectopic Adrenal Tissues-What are the Probable Mechanisms? J Clin Res Pediatr Endocrinol 2022; 14:258-266. [PMID: 34569220 PMCID: PMC9422908 DOI: 10.4274/jcrpe.galenos.2021.2021.0148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 09/21/2021] [Indexed: 12/01/2022] Open
Abstract
Ectopic adrenal tissue, defined as the formation of adrenal tissue in an abnormal anatomical location, is not a rare entity and may have clinical significance. Even though the mechanism for their emergence has not been fully understood, numerous cases of ectopic adrenal tissue have been reported, mostly in the vicinity of the original location of adrenal gland, such as in kidneys and gonads. In these cases, most authors attributed their emergence to a probable migration defect. However, this mechanism does not simply explain the ectopic tissues in remote locations, such as in the hypophysis or lungs. This review summarizes these reports, describing many different locations in which ectopic adrenal tissues were encountered, together with their suggested mechanisms.
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Affiliation(s)
- Gürkan Tarçın
- İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Department of Pediatric Endocrinology, İstanbul, Turkey
| | - Oya Ercan
- İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Department of Pediatric Endocrinology, İstanbul, Turkey
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27
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Parmar UM, Jalgaonkar MP, Kulkarni YA, Oza MJ. Autophagy-nutrient sensing pathways in diabetic complications. Pharmacol Res 2022; 184:106408. [PMID: 35988870 DOI: 10.1016/j.phrs.2022.106408] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Revised: 08/05/2022] [Accepted: 08/16/2022] [Indexed: 11/24/2022]
Abstract
The incidence of diabetes has been increasing in recent decades which is affecting the population of both, developed and developing countries. Diabetes is associated with micro and macrovascular complications which predominantly result from hyperglycemia and disrupted metabolic pathways. Persistent hyperglycemia leads to increased reactive oxygen species (ROS) generation, formation of misfolded and abnormal proteins, and disruption of normal cellular functioning. The inability to maintain metabolic homeostasis under excessive energy and nutrient input, which induces insulin resistance, is a crucial feature during the transition from obesity to diabetes. According to various study reports, redox alterations, intracellular stress and chronic inflammation responses have all been linked to dysregulated energy metabolism and insulin resistance. Autophagy has been considered a cleansing mechanism to prevent these anomalies and restore cellular homeostasis. However, disrupted autophagy has been linked to the pathogenesis of metabolic disorders such as obesity and diabetes. Recent studies have reported that the regulation of autophagy has a beneficial role against these conditions. When there is plenty of food, nutrient-sensing pathways activate anabolism and storage, but the shortage of food activates homeostatic mechanisms like autophagy, which mobilises internal stockpiles. These nutrient-sensing pathways are well conserved in eukaryotes and are involved in the regulation of autophagy which includes SIRT1, mTOR and AMPK. The current review focuses on the role of SIRT1, mTOR and AMPK in regulating autophagy and suggests autophagy along with these nutrient-sensing pathways as potential therapeutic targets in reducing the progression of various diabetic complications.
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Affiliation(s)
- Urvi M Parmar
- SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai 400056, India
| | - Manjiri P Jalgaonkar
- SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai 400056, India
| | - Yogesh A Kulkarni
- Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, Mumbai 400056, India
| | - Manisha J Oza
- SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai 400056, India.
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28
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Sahba K, Berk L, Bussell M, Lohman E, Zamora F, Gharibvand L. Treating peripheral neuropathy in individuals with type 2 diabetes mellitus with intraneural facilitation: a single blind randomized control trial. J Int Med Res 2022; 50:3000605221109390. [PMID: 35922961 PMCID: PMC9358562 DOI: 10.1177/03000605221109390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Objective To evaluate the effectiveness of intraneural facilitation (INF) for the treatment of diabetic peripheral neuropathy (DPN). Methods This single-blind, randomized clinical trial enrolled patients with type 2 diabetes mellitus and moderate-to-severe DPN symptoms below the ankle. Patients were randomly assigned to receive INF or sham treatment. In the INF group, trained INF physical therapists provided therapy for 50–60 min, three times a week for 3 weeks. Sham treatment consisted of patients believing they received anodyne therapy for 3 weeks. Pre- and post-treatment data were compared between the two groups for quality of life, balance, gait, protective sensory function and pain outcome measures. Results A total of 28 patients (17 males) were enrolled in the study (INF group n = 17; sham group n = 11). There was a significant decrease in the overall pain score in both the INF and sham groups over time, but the decrease was greater in the INF group (1.11 versus 0.82). Between-group comparisons demonstrated significant differences in unpleasant pain and protective sensory function. The INF group showed post-treatment improvements in protective sensory function and composite static balance score. Conclusions INF treatment improved pain perception, the composite static balance score and protective sensations in patients with DPN. Research Registry number: CNCT04025320
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Affiliation(s)
- Kyan Sahba
- Department of Allied Health Studies, School of Allied Health Professions, Loma Linda University, Loma Linda, CA, USA
| | - Lee Berk
- Department of Allied Health Studies, School of Allied Health Professions, Loma Linda University, Loma Linda, CA, USA.,Department of Pathology and Human Anatomy, School of Medicine, Loma Linda University, Loma Linda, CA, USA
| | - Mark Bussell
- Neuropathic Therapy Center, Loma Linda University Health, Loma Linda, CA, USA
| | - Everett Lohman
- Department of Physical Therapy, School of Allied Health Professions, Loma Linda University, Loma Linda, CA, USA
| | - Francis Zamora
- Department of Allied Health Studies, School of Allied Health Professions, Loma Linda University, Loma Linda, CA, USA
| | - Lida Gharibvand
- Department of Allied Health Studies, School of Allied Health Professions, Loma Linda University, Loma Linda, CA, USA
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29
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Huo J, Xue Y, Dong X, Lv J, Wu L, Gao H, Yang X, Liu H, Gao Q. Efficacy of vitamin and antioxidant supplements for treatment of diabetic peripheral neuropathy: systematic review and meta-analysis of randomized controlled trials. Nutr Neurosci 2022:1-18. [PMID: 35816410 DOI: 10.1080/1028415x.2022.2090606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
ABSTRACTThe results of treatment effect of vitamin or antioxidant intake on diabetic peripheral neuropathy (DPN) was inconsistent. Therefore, we performed a meta-analysis of randomized controlled trials (RCTs) to examine whether these supplements are effective in DPN treatment. We searched seven databases from inception to October 2021. All RCTs of DPN treatments with vitamin and antioxidant supplements were included. We performed sensitivity and subgroup analysis, and also tested for publication bias by the funnel plot and Egger's test. A total of 14 studies with 1384 patients were included in this systematic review. Three high-quality trials showed that vitamin and antioxidant supplements significantly increased sensory nerve conduction velocity (SNCV) of the sural nerve (MD = 2.66, 95%CI (0.60, 4.72), P < 0.05, I2 = 0%). Seven studies (758 participants) suggested that these supplements might have improvement on motor nerve conduction velocity (MNCV) of the peroneal nerve in DPN patients with the random-effect model (MD = 0.60, 95%CI (0.28, 0.92), P < 0.05, I2 = 65%). In four studies, these supplements could have improved on MNCV of the median nerve with the fixed-effect model (MD = 4.22, 95%CI (2.86, 5.57), P < 0.05, I2 = 0%). However, ten studies (841 participants) have suggested that vitamin and antioxidant supplements have not decreased glycosylated haemoglobin (HbA1c). Vitamin and antioxidant supplements may improve the conduction velocity of nerves, including median, sural and peroneal nerves of patients with DPN. But these supplements have not decreased HbA1c in DPN patients. Several trials with a large sample size are needed to provide evidence support for clinical practice in the future.
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Affiliation(s)
- Jinghong Huo
- School of Public Health and Management, Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, People's Republic of China.,Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, People's Republic of China
| | - Yanzhong Xue
- School of Public Health and Management, Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, People's Republic of China.,Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, People's Republic of China
| | - Xiaoying Dong
- Department of Endocrinology, General Hospital of Ningxia Medical University, Yinchuan, People's Republic of China
| | - Jinming Lv
- Department of Neuroelectrophysiology, General Hospital of Ningxia Medical University, Yinchuan, People's Republic of China
| | - Lingyu Wu
- School of Public Health and Management, Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, People's Republic of China.,Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, People's Republic of China
| | - Hua Gao
- Department of Pharmacy, General Hospital of Ningxia Medical University, Yinchuan, People's Republic of China
| | - Xiuqin Yang
- Department of Endocrinology, General Hospital of Ningxia Medical University, Yinchuan, People's Republic of China
| | - Huanhuan Liu
- Department of Endocrinology, General Hospital of Ningxia Medical University, Yinchuan, People's Republic of China
| | - Qinghan Gao
- School of Public Health and Management, Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, People's Republic of China.,Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, People's Republic of China
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Empagliflozin mitigates type 2 diabetes-associated peripheral neuropathy: a glucose-independent effect through AMPK signaling. Arch Pharm Res 2022; 45:475-493. [PMID: 35767208 PMCID: PMC9325846 DOI: 10.1007/s12272-022-01391-5] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Accepted: 06/07/2022] [Indexed: 12/30/2022]
Abstract
Diabetic peripheral neuropathy (DPN) represents a severe microvascular condition that dramatically affects diabetic patients despite adequate glycemic control, resulting in high morbidity. Thus, recently, anti-diabetic drugs that possess glucose-independent mechanisms attracted attention. This work aims to explore the potentiality of the selective sodium-glucose cotransporter-2 inhibitor, empagliflozin (EMPA), to ameliorate streptozotocin-induced DPN in rats with insight into its precise signaling mechanism. Rats were allocated into four groups, where control animals received vehicle daily for 2 weeks. In the remaining groups, DPN was elicited by single intraperitoneal injections of freshly prepared streptozotocin and nicotinamide (52.5 and 50 mg/kg, respectively). Then EMPA (3 mg/kg/p.o.) was given to two groups either alone or accompanied with the AMPK inhibitor dorsomorphin (0.2 mg/kg/i.p.). Despite the non-significant anti-hyperglycemic effect, EMPA improved sciatic nerve histopathological alterations, scoring, myelination, nerve fibers’ count, and nerve conduction velocity. Moreover, EMPA alleviated responses to different nociceptive stimuli along with improved motor coordination. EMPA modulated ATP/AMP ratio, upregulated p-AMPK while reducing p-p38 MAPK expression, p-ERK1/2 and consequently p-NF-κB p65 as well as its downstream mediators (TNF-α and IL-1β), besides enhancing SOD activity and lowering MDA content. Moreover, EMPA downregulated mTOR and stimulated ULK1 as well as beclin-1. Likewise, EMPA reduced miR-21 that enhanced RECK, reducing MMP-2 and -9 contents. EMPA’s beneficial effects were almost abolished by dorsomorphin administration. In conclusion, EMPA displayed a protective effect against DPN independently from its anti-hyperglycemic effect, probably via modulating the AMPK pathway to modulate oxidative and inflammatory burden, extracellular matrix remodeling, and autophagy.
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Abdelkader NF, Elbaset MA, Moustafa PE, Ibrahim SM. Empagliflozin mitigates type 2 diabetes-associated peripheral neuropathy: a glucose-independent effect through AMPK signaling. Arch Pharm Res 2022. [PMID: 35767208 DOI: 10.1007/s12272-022-01391-5/figures/1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/30/2023]
Abstract
Diabetic peripheral neuropathy (DPN) represents a severe microvascular condition that dramatically affects diabetic patients despite adequate glycemic control, resulting in high morbidity. Thus, recently, anti-diabetic drugs that possess glucose-independent mechanisms attracted attention. This work aims to explore the potentiality of the selective sodium-glucose cotransporter-2 inhibitor, empagliflozin (EMPA), to ameliorate streptozotocin-induced DPN in rats with insight into its precise signaling mechanism. Rats were allocated into four groups, where control animals received vehicle daily for 2 weeks. In the remaining groups, DPN was elicited by single intraperitoneal injections of freshly prepared streptozotocin and nicotinamide (52.5 and 50 mg/kg, respectively). Then EMPA (3 mg/kg/p.o.) was given to two groups either alone or accompanied with the AMPK inhibitor dorsomorphin (0.2 mg/kg/i.p.). Despite the non-significant anti-hyperglycemic effect, EMPA improved sciatic nerve histopathological alterations, scoring, myelination, nerve fibers' count, and nerve conduction velocity. Moreover, EMPA alleviated responses to different nociceptive stimuli along with improved motor coordination. EMPA modulated ATP/AMP ratio, upregulated p-AMPK while reducing p-p38 MAPK expression, p-ERK1/2 and consequently p-NF-κB p65 as well as its downstream mediators (TNF-α and IL-1β), besides enhancing SOD activity and lowering MDA content. Moreover, EMPA downregulated mTOR and stimulated ULK1 as well as beclin-1. Likewise, EMPA reduced miR-21 that enhanced RECK, reducing MMP-2 and -9 contents. EMPA's beneficial effects were almost abolished by dorsomorphin administration. In conclusion, EMPA displayed a protective effect against DPN independently from its anti-hyperglycemic effect, probably via modulating the AMPK pathway to modulate oxidative and inflammatory burden, extracellular matrix remodeling, and autophagy.
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Affiliation(s)
- Noha F Abdelkader
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo, 11562, Egypt.
| | - Marawan A Elbaset
- Medical Research and Clinical Studies Institute, Pharmacology, National Research Centre, Giza, Egypt
| | - Passant E Moustafa
- Medical Research and Clinical Studies Institute, Pharmacology, National Research Centre, Giza, Egypt
| | - Sherehan M Ibrahim
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo, 11562, Egypt
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Chitneni A, Rupp A, Ghorayeb J, Abd-Elsayed A. Early Detection of Diabetic Peripheral Neuropathy by fMRI: An Evidence-Based Review. Brain Sci 2022; 12:brainsci12050557. [PMID: 35624944 PMCID: PMC9139132 DOI: 10.3390/brainsci12050557] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 04/24/2022] [Accepted: 04/26/2022] [Indexed: 01/13/2023] Open
Abstract
With the significant rise in the prevalence of diabetes worldwide, diabetic peripheral neuropathy (DPN) remains the most common complication among type 1 and 2 diabetics. The adverse sequelae of DPN, which include neuropathic pain, diabetic foot ulcers and lower-limb amputations, significantly impact quality of life and are major contributors to the biopsychosocial and economic burden of diabetes at the individual, societal and health system levels. Because DPN is often diagnosed in the late stages of disease progression by electromyography (EMG), and neuropathic pain as a result of DPN is difficult to treat, the need for earlier detection is crucial to better ascertain and manage the condition. Among the various modalities available to aid in the early detection of DPN, functional magnetic resonance imaging (fMRI) has emerged as a practical tool in DPN imaging due to its noninvasive radiation-free nature and its ability to relate real-time functional changes reflecting the local oxygen consumption of regions of the CNS due to external stimuli. This review aims to summarize the current body of knowledge regarding the utility of fMRI in detecting DPN by observing central nervous system (CNS) activity changes among individuals with DPN when compared to controls. The evidence to date points toward a tendency for increased activity in various central neuroanatomical structures that can be detected by fMRI and positively correlates with diabetic neuropathic pain.
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Affiliation(s)
- Ahish Chitneni
- Department of Rehabilitation and Regenerative Medicine, NewYork-Presbyterian Hospital—Columbia and Cornell, New York, NY 10065, USA
- Correspondence: (A.C.); (A.A.-E.); Tel.: +1-608-263-6039 (A.A.-E.)
| | - Adam Rupp
- Department of Physical Medicine and Rehabilitation, University of Kansas Health System, Kansas City, MO 66160, USA;
| | - Joe Ghorayeb
- Department of Physical Medicine and Rehabilitation, University of Medicine & Health Sciences, New York, NY 10001, USA;
| | - Alaa Abd-Elsayed
- Department of Anesthesia, Division of Pain Medicine, School of Medicine & Public Health, University of Wisconsin, Madison, WI 53726, USA
- Correspondence: (A.C.); (A.A.-E.); Tel.: +1-608-263-6039 (A.A.-E.)
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Zhu J, Li W, Shi C, Li Q. A pharmacoeconomic evaluation of the pharmacotherapeutic options for painful diabetic neuropathy. Expert Opin Pharmacother 2022; 23:551-559. [PMID: 35084270 DOI: 10.1080/14656566.2022.2032647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Painful diabetic neuropathy (PDN) is a high incidence and severe complication of diabetes mellitus, significantly compromising patients' quality of life and causing tremendous economic burden. Considering drug costs becomes part of treatment decisions, with the growing choice of monotherapy or combination treatment strategies for PDN treatment. AREAS COVERED This systematic review aims to identify the cost-effectiveness of pharmacotherapies in PDN, summarize key findings, and assess the quality of studies to inform healthcare resource allocation decisions and future research. Economic evaluations were identified by searching PubMed, Web of Science, Scopus and health technology assessment (HTA) databases, as well as screening reference lists of previously identified studies. Relevant data was extracted, and the CHEERS checklist was used to assess the quality of the studies. EXPERT OPINION Collectively, the findings indicate that more pharmacoeconomics research is urgently needed to directly compare high-quality research for PDN combination medication/sequential treatment, and which is performed from a societal perspective. Simultaneously, to strengthen the reliability of the analysis, metrics such as adherence, incidence of adverse drug reactions, and pain levels utility value should be examined to verify the robustness of the basic results.
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Affiliation(s)
- Jiejin Zhu
- Department of Clinical Pharmacy, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Wanshu Li
- Department of Clinical Pharmacy, Ningbo Municipal Hospital of Traditional Chinese Medicine, Ningbo, Zhejiang, China
| | - Changcheng Shi
- Department of Clinical Pharmacy, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Qingyu Li
- Department of Clinical Pharmacy, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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Sloan G, Alam U, Selvarajah D, Tesfaye S. The Treatment of Painful Diabetic Neuropathy. Curr Diabetes Rev 2022; 18:e070721194556. [PMID: 34238163 DOI: 10.2174/1573399817666210707112413] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 02/18/2021] [Accepted: 03/08/2021] [Indexed: 11/22/2022]
Abstract
Painful diabetic peripheral neuropathy (painful-DPN) is a highly prevalent and disabling condition, affecting up to one-third of patients with diabetes. This condition can have a profound impact resulting in a poor quality of life, disruption of employment, impaired sleep, and poor mental health with an excess of depression and anxiety. The management of painful-DPN poses a great challenge. Unfortunately, currently there are no Food and Drug Administration (USA) approved disease-modifying treatments for diabetic peripheral neuropathy (DPN) as trials of putative pathogenetic treatments have failed at phase 3 clinical trial stage. Therefore, the focus of managing painful- DPN other than improving glycaemic control and cardiovascular risk factor modification is treating symptoms. The recommended treatments based on expert international consensus for painful- DPN have remained essentially unchanged for the last decade. Both the serotonin re-uptake inhibitor (SNRI) duloxetine and α2δ ligand pregabalin have the most robust evidence for treating painful-DPN. The weak opioids (e.g. tapentadol and tramadol, both of which have an SNRI effect), tricyclic antidepressants such as amitriptyline and α2δ ligand gabapentin are also widely recommended and prescribed agents. Opioids (except tramadol and tapentadol), should be prescribed with caution in view of the lack of definitive data surrounding efficacy, concerns surrounding addiction and adverse events. Recently, emerging therapies have gained local licenses, including the α2δ ligand mirogabalin (Japan) and the high dose 8% capsaicin patch (FDA and Europe). The management of refractory painful-DPN is difficult; specialist pain services may offer off-label therapies (e.g. botulinum toxin, intravenous lidocaine and spinal cord stimulation), although there is limited clinical trial evidence supporting their use. Additionally, despite combination therapy being commonly used clinically, there is little evidence supporting this practise. There is a need for further clinical trials to assess novel therapeutic agents, optimal combination therapy and existing agents to determine which are the most effective for the treatment of painful-DPN. This article reviews the evidence for the treatment of painful-DPN, including emerging treatment strategies such as novel compounds and stratification of patients according to individual characteristics (e.g. pain phenotype, neuroimaging and genotype) to improve treatment responses.
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Affiliation(s)
- Gordon Sloan
- Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, NHS Foundation Trust, Sheffield, UK
| | - Uazman Alam
- Department of Cardiovascular and Metabolic Medicine and the Pain Research Institute, Institute of Life Course and Medical Sciences, University of Liverpool, and Liverpool University Hospital, NHS Foundation Trust, Liverpool, UK
- Division of Diabetes, Endocrinology and Gastroenterology, Institute of Human Development, University of Manchester, Manchester, UK
| | - Dinesh Selvarajah
- Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, NHS Foundation Trust, Sheffield, UK
- Department of Oncology and Human Metabolism, University of Sheffield, Sheffield, UK
| | - Solomon Tesfaye
- Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, NHS Foundation Trust, Sheffield, UK
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Li X, Wang H, Zhou X, Ma D, Chai J, Liu J, Qian X, Chen C, Chen X. Acupuncture combine with Tuina for diabetic peripheral neuropathy: A protocol for a systematic review and meta-analysis. Medicine (Baltimore) 2021; 100:e28042. [PMID: 35049219 PMCID: PMC9191565 DOI: 10.1097/md.0000000000028042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 11/11/2021] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications of diabetes mellitus, with an incidence ranging from 60% to 90%. With the change in modern dietary structure, the incidence of diabetes is increasing year by year, and DPN is also on the rise. Acupuncture and Tuina treatments are often combined to treat DPN; however, there has been no meta-analysis on their synergistic effect; therefore, we aimed to perform a systematic review and meta-analysis to estimate the effectiveness of acupuncture combined with Tuina in DPN treatment. METHODS Nine electronic databases were retrieved for this study. The English databases mainly retrieved PubMed, Web of Science, Embase, AMED, and the Cochrane Library, while the CNKI, VIP, CBM, and Wanfang databases were used to retrieve the Chinese literature; there was no definite time limit for the retrieval literature, and the languages were limited to Chinese and English. We will consider articles published between database initiation and November 2021. We used Review Manager 5.4 software provided by the Cochrane Collaborative Network for statistical analysis. We then assessed the quality and risk of the included studies and observed the outcome measures. RESULTS This study provides a high-quality synthesis to assess the effectiveness and safety of acupuncture combined with Tuina for treating DPN. CONCLUSION This systematic review provided evidence to determine whether acupuncture combined with Tuina is an effective and safe intervention for patients with DPN. ETHICS AND DISSEMINATION The protocol for this systematic review does not require ethical approval because it does not involve humans. This article will be published in peer-reviewed journals and presented at relevant conferences. SYSTEMATIC REVIEW REGISTRATION INPLASY2021110017.
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Affiliation(s)
- Xuefeng Li
- Department of Acupuncture and Tuina, Changchun University of Chinese Medicine, Changchun, China
| | - Heran Wang
- Department of Acupuncture and Tuina, Changchun University of Chinese Medicine, Changchun, China
| | - Xue Zhou
- Department of Acupuncture and Tuina, Changchun University of Chinese Medicine, Changchun, China
| | - Dongyang Ma
- Department of Acupuncture and Tuina, Changchun University of Chinese Medicine, Changchun, China
| | - Jiapeng Chai
- Department of Acupuncture and Tuina, Changchun University of Chinese Medicine, Changchun, China
| | - Jiayi Liu
- Department of Acupuncture and Tuina, Changchun University of Chinese Medicine, Changchun, China
| | - Xin Qian
- Department of Acupuncture and Tuina, Changchun University of Chinese Medicine, Changchun, China
| | - Chunhai Chen
- Department of Acupuncture and Tuina, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China
| | - Xinhua Chen
- Department of Acupuncture and Tuina, Changchun University of Chinese Medicine, Changchun, China
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Zhang Y, Zhang S, Pan L, Wang B, Sun Y, Gao L, Wang L, Cui L, Zhang Q, Shang H, Jin S, Qin X, Geng D, Yu X, Yang L, Li L, Li Z, Yan C, Sun H, Sun T, Du B, Cao J, Hu F, Ma J, Zhou S, Zhao F, Li W, Zheng J, Yi Y, Xu J, Hu B, Sheng B, Li Z, Zhao Z, Yang T, Wang N, Zhao H, Mima D, Qu H, Wang Y, Song F, Li X, Li N, Fan D. Painful Diabetic Peripheral Neuropathy Study of Chinese Outpatients (PDNSCOPE): A Multicentre Cross-Sectional Registry Study of Clinical Characteristics and Treatment in Mainland China. Pain Ther 2021; 10:1355-1373. [PMID: 34363598 PMCID: PMC8586277 DOI: 10.1007/s40122-021-00281-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 06/10/2021] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION This aim of this study was to delineate current clinical scenarios of painful diabetic peripheral neuropathy (PDN) and associated anxiety and depression among patients in Mainland China, and to report current therapy and clinical practices. METHODS A total of 1547 participants were enrolled in the study between 14 June 2018 and 11 November 2019. Recruitment was conducted using a multilevel sampling method. Participants' demographics, medical histories, glucose parameters, Douleur Neuropathique 4 Questionnaire (DN4) scores, visual analogue scale (VAS) pain scores, Patient Health Questionnaire 9 (PHQ-9) scores, Generalised Anxiety Disorder 7 (GAD-7) scores and therapies were recorded. RESULTS The male-to-female ratio was 1.09:1 (807:740), and the mean age at onset was 61.28 ± 11.23 years. The mean DN4 score (± standard deviation) was 4.91 ± 1.88. The frequencies of DN4 sub-item phenotypes were: numbness, 81%; tingling, 68.71%; pins and needles, 62.90%; burning, 53.59%; hypoaesthesia to touch, 50.16%; electronic shocks, 43.31%; hypoaesthesia to pinprick, 37.94%; brushing, 37.82%; painful cold, 29.61%; and itching, 25.86%. Age, diabetic duration, depression history, PHQ-9 score and GAD-7 score were identified as risk factors for VAS pain score. Peripheral artery disease (PAD) was a protective factor for VAS pain score. For all participants currently diagnosed with PDN and for those previously diagnosed PDN, fasting blood glucose (FBG) was a risk factor for VAS; there was no association between FBG and VAS pain score for PDN diagnosed within 3 months prior to recruitment. Utilisation rate of opium therapies among enrolled participants was 0.71% , contradiction of first-line guideline recommendation for pain relief accounted for 9.43% (33/350) and contradiction of second-line guideline recommendation for opium dosage form was 0.57% (2/350). CONCLUSION Moderate to severe neuropathic pain in PDN was identified in 73.11% of participants. Age, diabetic duration, depression history, PHQ-9 score, GAD-7 score and FBG were risk factors for VAS pain scores. PAD was protective factor. The majority of pain relief therapies prescribed were in accordance with guidelines. TRIAL REGISTRATION ClinicalTrials.gov identifier, NCT03520608, retrospectively registered, 2018-05-11.
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Affiliation(s)
- Yuanjin Zhang
- Department of Neurology, Peking University Third Hospital, 49th North Garden Road, Haidian District, Beijing, China
| | - Shaowei Zhang
- Department of Endocrinology, Shenyang Weikang Hospital, Shenyang, China
| | - Liya Pan
- Department of Neurology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, China
| | - Baojun Wang
- Department of Neurology, Baotou Central Hospital, Baotou, China
| | - Yuanlin Sun
- Department of Neurology, Panjin Central Hospital, Panjin, China
| | - Lijun Gao
- Department of Neurology, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Ling Wang
- Department of Endocrinology, Fukuang General Hospital of Liaoning Health Industry Group, Fushun, China
| | - Lijuan Cui
- Department of Endocrinology, Bengang General Hospital of Liaoning Health Industry Group, Benxi, China
| | - Qing Zhang
- Department of Neurology, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Heng Shang
- Department of Gastroenterology, Cangzhou People's Hospital, Cangzhou, China
| | - Suqin Jin
- Department of Neurology, The Second Hospital of Shandong University, Jinan, China
| | - Xing Qin
- Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Deqin Geng
- Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Xiaorong Yu
- Department of Neurology, Linfen People's Hospital, Linfen, China
| | - Lin Yang
- Department of Neurology, The First Affiliated Hospital of Dali University, Dali, China
| | - Li Li
- Department of Gastroenterology, The First People's Hospital of Taian, Tai'an, China
| | - Zuoxiao Li
- Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Chaoli Yan
- Department of Endocrinology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Hongbin Sun
- Department of Neurology, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, Chengdu, China
| | - Tao Sun
- Pain Department, Shandong Provincial Hospital, Jinan, China
| | - Baoxin Du
- Department of Neurology, Guangdong Traditional Chinese Medicine Hospital, Guangzhou, China
| | - Junying Cao
- Department of Neurology, Tianjin Gangkou Hospital, Tianjin, China
| | - Fengyun Hu
- Department of Neurology, Shanxi Provincial People's Hospital, Taiyuan, China
| | - Jianhua Ma
- Department of Neurology, The First Affiliated Hospital of Xinjiang Medical University, Ürümqi, China
| | - Shengnian Zhou
- Department of Neurology, Qilu Hospital of Shandong University, Jinan, China
| | - Fengli Zhao
- Department of Neurology, Yuncheng Central Hospital, Yuncheng, China
| | - Wei Li
- Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China
| | - Jianming Zheng
- Department of Neurology, Mindong Hospital of Fujian Medical University, Ningde, China
| | - Yanhui Yi
- Department of Neurology, The Second People's Hospital of Hunan Province, Brain Hospital of Hunan Province, Changsha, China
| | - Jianguo Xu
- Department of Neurology, Guiyang Sixth Hospital, Guiyang, China
| | - Bo Hu
- Department of Neurology, Union Hospital, Tongji Medical Collage of Huazhong University of Science and Technology, Wuhan, China
| | - Baoying Sheng
- Department of Neurology, The First Affiliated Hospital of Jiamusi University, Jiamusi, China
| | - Zhaohui Li
- Department of Neurology, People's Hospital of Xinxing Country, Yunfu, China
| | - Zhong Zhao
- Department of Neurology, Suzhou Municipal Hospital, Suzhou, China
| | - Ting Yang
- Department of Neurology, Tianjin Xiqing Hospital, Tianjin, China
| | - Ni Wang
- Department of Neurology, Central Hospital of Wafangdian, Dalian, China
| | - Hongdong Zhao
- Department of Neurology, Nanjing First Hospital, Nanjing, China
| | - Dunzhu Mima
- Department of Neurology, Tibet Autonomous Region People's Hospital, Lhasa, China
| | - Huaiqian Qu
- Department of Neurology, Liaocheng People's Hospital, Liaocheng, China
| | - Yi Wang
- Department of Neurology, Huashan Hospital Fudan University, Shanghai, China
| | - Fuxia Song
- Department of Neurology, Yantai Yuhuangding Hospital, Yantai, China
| | - Xinyi Li
- Department of Neurology, Shanxi Bethune Hospital, Taiyuan, China
| | - Nan Li
- Research Center of Clinical Epidemiology, Peking University Third Hospital, 49th North Garden Road, Haidian District, Beijing, China.
| | - Dongsheng Fan
- Department of Neurology, Peking University Third Hospital, 49th North Garden Road, Haidian District, Beijing, China.
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Tocotrienol-Rich Vitamin E (Tocovid) Improved Nerve Conduction Velocity in Type 2 Diabetes Mellitus Patients in a Phase II Double-Blind, Randomized Controlled Clinical Trial. Nutrients 2021; 13:nu13113770. [PMID: 34836025 PMCID: PMC8618591 DOI: 10.3390/nu13113770] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 09/30/2021] [Accepted: 10/17/2021] [Indexed: 01/02/2023] Open
Abstract
Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of diabetes that affects approximately half of the diabetic population. Up to 53% of DPN patients experience neuropathic pain, which leads to a reduction in the quality of life and work productivity. Tocotrienols have been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties in preclinical and clinical studies. This study aimed to investigate the effects of tocotrienol-rich vitamin E (Tocovid SuprabioTM) on nerve conduction parameters and serum biomarkers among patients with type 2 diabetes mellitus (T2DM). A total of 88 patients were randomized to receive 200 mg of Tocovid twice daily, or a matching placebo for 12 months. Fasting blood samples were collected for measurements of HbA1c, renal profile, lipid profile, and biomarkers. A nerve conduction study (NCS) was performed on all patients at baseline and subsequently at 2, 6, 12 months. Patients were reassessed after 6 months of washout. After 12 months of supplementation, patients in the Tocovid group exhibited highly significant improvements in conduction velocity (CV) of both median and sural sensory nerves as compared to those in the placebo group. The between-intervention-group differences (treatment effects) in CV were 1.60 m/s (95% CI: 0.70, 2.40) for the median nerve and 2.10 m/s (95% CI: 1.50, 2.90) for the sural nerve. A significant difference in peak velocity (PV) was also observed in the sural nerve (2.10 m/s; 95% CI: 1.00, 3.20) after 12 months. Significant improvements in CV were only observed up to 6 months in the tibial motor nerve, 1.30 m/s (95% CI: 0.60, 2.20). There were no significant changes in serum biomarkers, transforming growth factor beta-1 (TGFβ-1), or vascular endothelial growth factor A (VEGF-A). After 6 months of washout, there were no significant differences from baseline between groups in nerve conduction parameters of all three nerves. Tocovid at 400 mg/day significantly improve tibial motor nerve CV up to 6 months, but median and sural sensory nerve CV in up to 12 months of supplementation. All improvements diminished after 6 months of washout.
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Lowenstern A, Sheridan P, Wang TY, Boero I, Vemulapalli S, Thourani VH, Leon MB, Peterson ED, Brennan JM. Sex disparities in patients with symptomatic severe aortic stenosis. Am Heart J 2021; 237:116-126. [PMID: 33722584 DOI: 10.1016/j.ahj.2021.01.021] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 01/28/2021] [Indexed: 12/31/2022]
Abstract
BACKGROUND We evaluated whether there is equitable distribution across sexes of treatment and outcomes for aortic valve replacement (AVR), via surgical (SAVR) or transcatheter (TAVR) methods, in symptomatic severe aortic stenosis (ssAS) patients. METHODS Using de-identified data, we identified 43,822 patients with ssAS (2008-2016). Multivariate competing risk models were used to determine the likelihood of any AVR, while accounting for the competing risk of death. Association between sex and 1-year mortality, stratified by AVR status, was evaluated using multivariate Cox regression models with AVR as a time-dependent variable. RESULTS Among patients with ssAS, 20,986 (47.9%) were female. Females were older (median age 81 vs. 78, P<0.001), more likely to have body mass index <20 (8.5% vs. 3.5%), and home oxygen use (4.4% vs. 3.4%, P<0001 for all). Overall, 12,129 (27.7%) patients underwent AVR for ssAS. Females were less likely to undergo AVR compared with males (24.1% vs. 31.0%, adjusted hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.77-0.83), but when treated, were more likely to undergo TAVR (37.9% vs. 30.9%, adjusted HR 1.21, 95% CI 1.15-1.27). Untreated females and males had similarly high rates of mortality at 1 year (31.1% vs. 31.3%, adjusted HR 0.98, 95% CI 0.94-1.03). Among those undergoing AVR, females had significantly higher mortality (10.2% vs. 9.4%, adjusted HR 1.24, 95% CI 1.10-1.41), driven by increased SAVR-associated mortality (9.0% vs. 7.6%, adjusted HR 1.43, 95% CI 1.21-1.69). CONCLUSIONS Treatment rates for ssAS patients remain suboptimal with disparities in female treatment.
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Affiliation(s)
- Angela Lowenstern
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC
| | - Paige Sheridan
- Department of Family Medicine and Public Health, University of San Diego, San Diego, CA; Boston Consulting Group, Boston, MA
| | - Tracy Y Wang
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC
| | | | | | - Vinod H Thourani
- Department of Cardiovascular Surgery, Marcus Valve Center, Piedmont Heart Institute, Atlanta, GA
| | - Martin B Leon
- Columbia University Medical Center and New York Presbyterian Hospital, New York, NY
| | - Eric D Peterson
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC
| | - J Matthew Brennan
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
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Yovera-Aldana M, Velásquez-Rimachi V, Huerta-Rosario A, More-Yupanqui MD, Osores-Flores M, Espinoza R, Gil-Olivares F, Quispe-Nolazco C, Quea-Vélez F, Morán-Mariños C, Pinedo-Torres I, Alva-Diaz C, Pacheco-Barrios K. Prevalence and incidence of diabetic peripheral neuropathy in Latin America and the Caribbean: A systematic review and meta-analysis. PLoS One 2021; 16:e0251642. [PMID: 33984049 PMCID: PMC8118539 DOI: 10.1371/journal.pone.0251642] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Accepted: 04/29/2021] [Indexed: 01/05/2023] Open
Abstract
AIMS The objective of this systematic review and meta-analysis is to estimate the prevalence and incidence of diabetic peripheral neuropathy (DPN) in Latin America and the Caribbean (LAC). MATERIALS AND METHODS We searched MEDLINE, SCOPUS, Web of Science, EMBASE and LILACS databases of published observational studies in LAC up to December 2020. Meta-analyses of proportions were performed using random-effects models using Stata Program 15.1. Heterogeneity was evaluated through sensitivity, subgroup, and meta-regression analyses. Evidence certainty was performed with the GRADE approach. RESULTS Twenty-nine studies from eight countries were included. The estimated prevalence of DPN was 46.5% (95%CI: 38.0-55.0) with a significant heterogeneity (I2 = 98.2%; p<0.01). Only two studies reported incidence, and the pooled effect size was 13.7% (95%CI: 10.6-17.2). We found an increasing trend of cumulative DPN prevalence over time. The main sources of heterogeneity associated with higher prevalence were diagnosis criteria, higher A1c (%), and inadequate sample size. We judge the included evidence as very low certainty. CONCLUSION The overall prevalence of DPN is high in LAC with significant heterogeneity between and within countries that could be explained by population type and methodological aspects. Significant gaps (e.g., under-representation of most countries, lack of incidence studies, and heterogenous case definition) were identified. Standardized and population-based studies of DPN in LAC are needed.
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Affiliation(s)
- Marlon Yovera-Aldana
- Grupo de Investigación Neurociencia, Efectividad y Salud Pública, Universidad Científica del Sur, Lima, Perú
| | - Victor Velásquez-Rimachi
- Grupo de Investigación Neurociencia, Efectividad y Salud Pública, Universidad Científica del Sur, Lima, Perú
- Red de Eficacia Clínica y Sanitaria, REDECS, Lima, Perú
- Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú
| | - Andrely Huerta-Rosario
- Grupo de Investigación Neurociencia, Efectividad y Salud Pública, Universidad Científica del Sur, Lima, Perú
- Red de Eficacia Clínica y Sanitaria, REDECS, Lima, Perú
- Facultad de Medicina Hipólito Unanue, Universidad Nacional Federico Villarreal, Lima, Perú
| | - M. D. More-Yupanqui
- Red de Eficacia Clínica y Sanitaria, REDECS, Lima, Perú
- Servicio de Patología, Departamento de Ayuda Diagnóstico, Hospital Daniel Alcides Carrión, Callao, Perú
| | - Mariela Osores-Flores
- Red de Eficacia Clínica y Sanitaria, REDECS, Lima, Perú
- Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú
| | - Ricardo Espinoza
- Escuela de Medicina, Universidad Peruana de Ciencias Aplicadas, Lima, Perú
| | - Fradis Gil-Olivares
- Red de Eficacia Clínica y Sanitaria, REDECS, Lima, Perú
- Unidad de Guías de Práctica Clínica, AUNA, Lima, Perú
| | | | - Flor Quea-Vélez
- Red de Eficacia Clínica y Sanitaria, REDECS, Lima, Perú
- Facultad de Ciencias de la Salud, Universidad Privada San Juan Bautista, Lima, Perú
| | - Christian Morán-Mariños
- Red de Eficacia Clínica y Sanitaria, REDECS, Lima, Perú
- Unidad de Investigación en Bibliometría, Vicerrectorado de Investigación, Universidad San Ignacio de Loyola, Lima, Perú
| | - Isabel Pinedo-Torres
- Grupo de Investigación Neurociencia, Efectividad y Salud Pública, Universidad Científica del Sur, Lima, Perú
- Red de Eficacia Clínica y Sanitaria, REDECS, Lima, Perú
- Servicio de Endocrinología, Departamento de Medicina y Oficina de Apoyo a la Docencia e Investigación (OADI), Hospital Daniel Alcides Carrín, Callao, Perú
| | - Carlos Alva-Diaz
- Grupo de Investigación Neurociencia, Efectividad y Salud Pública, Universidad Científica del Sur, Lima, Perú
- Red de Eficacia Clínica y Sanitaria, REDECS, Lima, Perú
- Servicio de Neurología, Departamento de Medicina y Oficina de Apoyo a la Docencia e Investigación (OADI), Hospital Daniel Alcides Carrión, Callao, Peru
| | - Kevin Pacheco-Barrios
- Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud, Universidad San Ignacio de Loyola, Lima, Perú
- Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
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Alyoubi RA, Alshareef AA, Aldughaither SM, Aljaroudi AM, Alabdulwahed A, Alduraibi FM, Masoud AT, Abu-Zaid A. Efficacy and safety of mirogabalin treatment in patients with diabetic peripheral neuropathic pain: A systematic review and meta-analysis of randomised controlled trials. Int J Clin Pract 2021; 75:e13744. [PMID: 32991782 DOI: 10.1111/ijcp.13744] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 09/02/2020] [Accepted: 09/23/2020] [Indexed: 12/12/2022] Open
Abstract
AIM We aimed to perform a systematic review and meta-analysis to examine the efficacy and safety of mirogabalin in patients with diabetic peripheral neuropathic pain (DPNP). METHODS We searched four databases from inception to 1st July 2020. We included all randomised controlled trials (RCTs) which assessed the effectiveness and safety of mirogabalin in patients with DPNP. We evaluated the quality of the included RCTs using the Cochrane risk of bias assessment tool. We pooled dichotomous outcomes as risk ratios and continuous outcomes as mean differences with 95% confidence intervals, both under the random- or fixed-effects model. RESULTS Three RCTs matched our inclusion criteria with a total of 1732 patients with DPNP: 1057, 534 and 141 patients received mirogabalin, placebo and pregabalin, respectively. The quality of included RCTs was marked as moderate-to-high. Mirogabalin treatment was significantly associated with a significant reduction in the average daily pain score (ADPS) compared with placebo over 7 weeks. Compared with pregabalin, mirogabalin was significantly associated with more decrease in ADPS only after 3, 4 and 5 weeks. The proportion of patients with ≥30% and ≥50% reduction in the ADPS was significantly higher in the mirogabalin vs placebo and pregabalin groups. Compared with placebo, mirogabalin was significantly associated with more adverse events of dizziness, increased weight, peripheral oedema and somnolence. The safety profile was comparable between mirogabalin and pregabalin. CONCLUSIONS Our systematic review and meta-analysis revealed that in patients with DPNP, mirogabalin treatment was superior to placebo and pregabalin in decreasing the ADPS over time. Besides, mirogabalin was largely safe and associated with some adverse events that could be managed conservatively.
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Affiliation(s)
- Reem Abdullah Alyoubi
- Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | | | | | - Abeer Mahdi Aljaroudi
- Department of Internal Medicine, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Alwaleed Alabdulwahed
- Department of Internal Medicine, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | | | | | - Ahmed Abu-Zaid
- Department of Internal Medicine, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
- Department of Pharmacology, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, TN, USA
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Xiaohua G, Dongdong L, Xiaoting N, Shuoping C, Feixia S, Huajun Y, Qi Z, Zimiao C. Severe Vitamin D Deficiency Is Associated With Increased Expression of Inflammatory Cytokines in Painful Diabetic Peripheral Neuropathy. Front Nutr 2021; 8:612068. [PMID: 33777989 PMCID: PMC7987807 DOI: 10.3389/fnut.2021.612068] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 02/18/2021] [Indexed: 12/13/2022] Open
Abstract
Background: The exact pathogenic mechanism of the painful diabetic peripheral neuropathy (DPN) is poorly understood. Our study aimed to evaluate the association amongst vitamin D status, inflammatory cytokines, and painful DPN. Methods: A total of 483 patients were divided into three groups, i.e., diabetes without DPN (no-DPN, n = 86), diabetes with painless DPN (painless DPN, n = 176) and diabetes with painful DPN (painful DPN, n = 221) groups. Basic information and laboratory results were collected. The concentrations of vitamin D (25-hydroxyvitamin D), high-sensitivity C-reactive protein, interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were also measured. Results: The prevalence of severe vitamin D deficiency (<10 ng/mL) was more common in the painful DPN group than in the painless DPN and no-DPN groups (25.8,12.5, and 8.1%, respectively, P < 0.01). Cases in the painful DPN group had significantly higher concentrations of IL-6 (P < 0.01) and TNF-α (P < 0.01) than those in the two other groups. The multivariate logistic analysis showed that severe vitamin D deficiency, IL-6, and TNF-α were independent risks for painful DPN after adjusting for confounding factors. Furthermore, the vitamin D status had significantly negative correlations with IL-6 (r = -0.56, P < 0.01) and TNF-α (r = -0.47, P < 0.01) levels. Conclusion: Severe vitamin D deficiency was an independent risk factor for the painful DPN. Severe vitamin D deficiency status may play a role in the painful DPN pathogenesis through elevated IL-6 and TNF-α levels.
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Affiliation(s)
- Gong Xiaohua
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Luo Dongdong
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Dalian Medical University, Dalian Medical University, Dalian, China
| | - Niu Xiaoting
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Chen Shuoping
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Shen Feixia
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yang Huajun
- Songqiao Hospital of Wanquan Town, Wenzhou, China
| | - Zhou Qi
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Chen Zimiao
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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Zhou L, Bhattacharjee S, Kwoh CK, Malone DC, Tighe PJ, Reisfield GM, Slack M, Wilson DL, Lo-Ciganic WH. Association Between Dual Trajectories of Opioid and Gabapentinoid Use and Healthcare Expenditures Among US Medicare Beneficiaries. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2021; 24:196-205. [PMID: 33518026 PMCID: PMC8359825 DOI: 10.1016/j.jval.2020.12.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 11/30/2020] [Accepted: 12/08/2020] [Indexed: 06/12/2023]
Abstract
OBJECTIVES Little is known about relationships between opioid- and gabapentinoid-use patterns and healthcare expenditures that may be affected by pain management and risk of adverse outcomes. This study examined the association between patients' opioid and gabapentinoid prescription filling/refilling trajectories and direct medical expenditures in US Medicare. METHODS This cross-sectional study included a 5% national sample (2011-2016) of fee-for-service beneficiaries with fibromyalgia, low back pain, neuropathy, or osteoarthritis newly initiating opioids or gabapentinoids. Using group-based multitrajectory modeling, this study identified patients' distinct opioid and gabapentinoid (OPI-GABA) dose and duration patterns, based on standardized daily doses, within a year of initiating opioids and/or gabapentinoids. Concurrent direct medical expenditures within the same year were estimated using inverse probability of treatment weighted multivariable generalized linear regression, adjusting for sociodemographic and health status factors. RESULTS Among 67 827 eligible beneficiaries (mean age ± SD = 63.6 ± 14.8 years, female = 65.8%, white = 77.1%), 11 distinct trajectories were identified (3 opioid-only, 4 gabapentinoid-only, and 4 concurrent OPI-GABA trajectories). Compared with opioid-only early discontinuers ($13 830, 95% confidence interval = $13 643-14 019), gabapentinoid-only early discontinuers and consistent low-dose and moderate-dose gabapentinoid-only users were associated with 11% to 23% lower health expenditures (adjusted mean expenditure = $10 607-$11 713). Consistent low-dose opioid-only users, consistent high-dose opioid-only users, consistent low-dose OPI-GABA users, consistent low-dose opioid and high-dose gabapentinoid users, and consistent high-dose opioid and moderate-dose gabapentinoid users were associated with 14% to 106% higher healthcare expenditures (adjusted mean expenditure = $15 721-$28 464). CONCLUSIONS Dose and duration patterns of concurrent OPI-GABA varied substantially among fee-for-service Medicare beneficiaries. Consistent opioid-only users and all concurrent OPI-GABA users were associated with higher healthcare expenditures compared to opioid-only discontinuers.
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Affiliation(s)
- Lili Zhou
- Department of Pharmacy Practice and Science, University of Arizona, Tucson, AZ, USA; University of Arizona Arthritis Center, Tucson, AZ, USA
| | | | - C Kent Kwoh
- University of Arizona Arthritis Center, Tucson, AZ, USA; Department of Medicine, University of Arizona, Tucson, AZ, USA
| | - Daniel C Malone
- Department of Pharmacotherapy, University of Utah, Salt Lake City, UT, USA
| | - Patrick J Tighe
- Department of Anesthesiology, University of Florida, Gainesville, FL, USA
| | - Gary M Reisfield
- Divisions of Addiction Medicine & Forensic Psychiatry, Departments of Psychiatry & Anesthesiology, University of Florida, Gainesville, FL, USA
| | - Marion Slack
- Department of Pharmacy Practice and Science, University of Arizona, Tucson, AZ, USA
| | - Debbie L Wilson
- Department of Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, FL, USA
| | - Wei-Hsuan Lo-Ciganic
- Department of Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, FL, USA; Center for Drug Evaluation and Safety, University of Florida, Gainesville, FL, USA.
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Yu B, Li M, Huang H, Ma S, Huang K, Zhong Z, Yu S, Zhang L. Acupuncture treatment of diabetic peripheral neuropathy: An overview of systematic reviews. J Clin Pharm Ther 2021; 46:585-598. [PMID: 33511675 PMCID: PMC8247887 DOI: 10.1111/jcpt.13351] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 11/30/2020] [Accepted: 12/21/2020] [Indexed: 12/16/2022]
Abstract
What is known and objective To evaluate the clinical efficacy of acupuncture through a review and analysis of systematic reviews of acupuncture for the treatment of diabetic peripheral neuropathy. Methods Systematic reviews of acupuncture treatment for diabetic peripheral neuropathy were collected by searching CNKI, VIP, Wanfang database, Chinese Biomedical Literature Database (CBM), PubMed, Web of Science and the Cochrane Library. The retrieval period was from the establishment of the database to February 14, 2020. After literature selection and extraction, included reports were evaluated in terms of the quality of the methodology and of the report using criteria from the AMSTAR2 scale and the PRISMA statement. Results and discussion Eighty eight reviews were retrieved. The inclusion criteria were a published systematic evaluation/meta‐analysis/systematic review of acupuncture treatment for diabetic peripheral neuropathy, which included subjects meeting the diagnostic criteria for diabetic peripheral neuropathy, and which compared acupuncture treatment with non‐acupuncture treatment. After the inclusion criteria had been applied, 18 reviews were finally included. According to the PRISMA statement, 3 reports were relatively complete, 12 reports had certain defects, 3 reports had considerable information missing, and 18 reports had extremely low methodological quality according to the AMSTAR2 scale. Current evidence shows that acupuncture improves diabetic peripheral neuropathy and increases nerve conduction velocity. However, the methodological quality of the reviews is generally extremely low, and most of the reviews had certain defects, showing that there is still much room for improvement in terms of the methodology and quality of the research reports. What is new and conclusion Acupuncture appears to have an effect on DPN, effectively improving nerve conduction and clinical symptoms. Although the methodological quality of the included studies was generally very low and defects were frequent, our study highlights areas where improvement in methodology is required. There is a need for further study of the pathogenesis of DPN, and for developing a unified standard for methods of acupuncture treatment, acupoint selection, and adverse reactions reporting. Traditional Chinese medical practices such as acupuncture should adopt an evidence‐based approach to provide greater confidence in their use. This review evaluates and verifies the efficacy of acupuncture in the treatment of diabetic peripheral neuropathy by using the quality of report and methodology, in order to provide reference for clinical decision‐making.
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Affiliation(s)
- Bin Yu
- Changchun University of Chinese Medicine, Changchun Jilin, China
| | - MengYuan Li
- Changchun University of Chinese Medicine, Changchun Jilin, China
| | - HaiPeng Huang
- Changchun University of Chinese Medicine, Changchun Jilin, China
| | - ShiQi Ma
- Changchun University of Chinese Medicine, Changchun Jilin, China
| | - Ke Huang
- Changchun University of Chinese Medicine, Changchun Jilin, China
| | - Zhen Zhong
- Changchun University of Chinese Medicine, Changchun Jilin, China
| | - Shuo Yu
- Changchun University of Chinese Medicine, Changchun Jilin, China
| | - LiYing Zhang
- Changchun University of Chinese Medicine, Changchun Jilin, China
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Freynhagen R, Baron R, Kawaguchi Y, Malik RA, Martire DL, Parsons B, Rey RD, Schug SA, Jensen TS, Tölle TR, Ushida T, Whalen E. Pregabalin for neuropathic pain in primary care settings: recommendations for dosing and titration. Postgrad Med 2021; 133:1-9. [PMID: 33423590 DOI: 10.1080/00325481.2020.1857992] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Pregabalin is one of the first-line treatments approved for the management of neuropathic pain (NeP). While many patients benefit from treatment with pregabalin, they are often treated with suboptimal doses, possibly due to unfamiliarity around prescribing the drug and/or side effects that can occur with up-titration. This narrative review discusses key aspects of initiating, titrating, and managing patients prescribed pregabalin therapy, and addresses concerns around driving and the potential for abuse, as well as when to seek specialist opinion. To ensure that patients derive maximum therapeutic benefit from the drug, we suggest a 'low and slow' dosing approach to limit common side effects and optimize tolerability alongside patients' expectations. When requiring titration to higher doses, we recommend initiating 'asymmetric dosing,' with the larger dose in the evening. Fully engaging patients in order for them to understand the expected timeline for efficacy and side effects (including their resolution), can also help determine the optimal titration tempo for each individual patient. The 'low and slow' approach also recognizes that patients with NeP are heterogeneous in terms of their optimal therapeutic dose of pregabalin. Hence, it is recommended that general practitioners closely monitor patients and up-titrate according to pain relief and side effects to limit suboptimal dosing or premature discontinuation.
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Affiliation(s)
- Rainer Freynhagen
- Center for Anaesthesiology, Intensive Care, Pain Medicine & Palliative Medicine, Benedictus Hospital, Feldafing, Germany
| | - Ralf Baron
- Department of Anaesthesiology, Technische Universtät München, Munich, Germany
| | - Yoshiharu Kawaguchi
- Division of Neurological Pain Research and Therapy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Rayaz A Malik
- Department of Orthopaedic Surgery, Toyama University Hospital, Toyama, Japan; eWeill Cornell Medicine, Qatar, Doha, Qatar
| | | | | | | | - Stephan A Schug
- Argentine Institute for Neurological Research (IADIN), Buenos Aires, Argentina
| | | | - Thomas R Tölle
- Anaesthesiology and Pain Medicine, Medical School, University of Western Australia, Perth, WA, Australia
| | - Takahiro Ushida
- Department of Neurology and Diabetic Neuropathy Consortium, Aarhus University Hospital, Aarhus, Denmark
| | - Ed Whalen
- Department of Neurology, Technische Universität München, Munich, Germany.,Multidisciplinary Pain Center, Aichi Medical University Hospital, Nagakute, Japan
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Tseng CH, Chong CK, Sheu JJ. Prevalence and Risk Factors of Sensory Symptoms in Diabetes Patients in Taiwan. Front Endocrinol (Lausanne) 2021; 11:580426. [PMID: 33488515 PMCID: PMC7821276 DOI: 10.3389/fendo.2020.580426] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Accepted: 11/26/2020] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Diabetic sensory neuropathy has rarely been studied in the Asian populations. This study investigated the prevalence and risk factors of sensory symptoms (SS) in the Taiwanese diabetes patients. METHODS A total of 1,400 diabetes patients received a health examination together with a structured questionnaire interview for three categories of abnormal sensation of numbness or tingling pain, electric shock, and skin thickness sensation on seven anatomical sites on upper limbs and six sites on lower limbs. Prevalence of SS was defined using nine different criteria, with the least stringent criterion of "any positive symptom on at least 1 site" and the most stringent criterion of "any positive symptom on at least bilateral and symmetrical 2 sites involving the lower limb." Logistic regression was used to estimate the odds ratios and their 95% confidence interval for SS by the different definitions. Fasting plasma glucose and hemoglobin A1c were entered in separate models to avoid hypercollinearity. RESULTS The prevalence of SS was 14.4 and 54.0% when using the most stringent and least stringent criterion, respectively. Women consistently had a significantly higher prevalence than men did. Among the three categories of symptoms, numbness or tingling pain was the most common, and fingers and toes were the most commonly involved anatomical sites. For any symptoms, 37.1% of the patients had any symptoms on the upper limbs and 41.7% had any symptoms on the lower limbs. Female sex, diabetes duration, hemoglobin A1c, and hypertension were associated with SS in all models. CONCLUSIONS Taiwanese diabetes patients may have a high prevalence of SS if a structured questionnaire is used for screening. Female sex, diabetes duration, hemoglobin A1c, and hypertension are associated with SS.
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Affiliation(s)
- Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Division of Environmental Health and Occupational Medicine of the National Health Research Institutes, Zhunan, Taiwan
| | - Choon-Khim Chong
- Chong’s Physical Medicine and Rehabilitation Center, Taipei, Taiwan
| | - Jau-Jiuan Sheu
- Department of Neurology, Taipei Medical University Hospital, Taipei, Taiwan
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Tadesse DB, Gebrewahd GT, Hailay A, Aberhe W, Mebrahtom G, Zereabruk K, Gebreayezgi G, Mariye T, Haile TG, Gebremeskel GG, Demoz GT. Diabetic Peripheral Neuropathy in Ethiopia: A Systematic Review and Meta-Analysis. J Diabetes Res 2021; 2021:5304124. [PMID: 33628833 PMCID: PMC7880716 DOI: 10.1155/2021/5304124] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 10/31/2020] [Accepted: 11/02/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Currently, diabetic peripheral neuropathy (DPN) is one of the most severe complications of diabetes mellitus (DM). Despite the seriousness of this problem, limited evidence is available on the prevalence of diabetic peripheral neuropathy among patients with diabetes mellitus in Ethiopia. In Ethiopia, there were no updated studies that estimate the national prevalence of DPN. Hence, this systematic review and meta-analysis provided a national prevalence of diabetic peripheral neuropathy among patients with diabetes mellitus in Ethiopia. METHODS This study was submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO) in March 2020 and accepted with the registration number CRD42020173831. Different database searching engines were searched online to retrieve related articles, including PubMed, Scopus, Google Scholar, African Journals Online, World Health Organization (WHO) Afro Library, and Cochrane Review. The reviewers used the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guideline in the reviewing process. In this systematic review and meta-analysis, all published and unpublished articles were analyzed. The reviewers used the random effects model to estimate the pooled prevalence of diabetic peripheral neuropathy among diabetes mellitus patients. The reviewers conducted the statistical analysis using the R version 3.5.3 and RStudio version 1.2.5033 software for Windows. The reviewers evaluated the heterogeneity across the included studies by the inconsistency index (I 2). The reviewers examined the publication bias by the funnel plot. RESULTS The search of the databases produced 245 papers. After checking the inclusion and exclusion criteria, 38 articles with 14029 total patients with diabetes mellitus were found suitable for the review. Except for three (retrospective cohort study), all studies were cross-sectional. The overall pooled prevalence of diabetic peripheral neuropathy was 22% (95% CI 18% to 26%). The subgroup analysis of diabetic peripheral neuropathy among patients with diabetes in the different regions was 23% (95% CI 17% to 29%) in Addis Ababa, 27% (95% CI 16% to 38%) in Oromia, 16% (95% CI 14% to 18%) in South nation and nationalities, and 15% (95% CI 6% to 24%) in Amhara. CONCLUSIONS More than one-fifth of patients with diabetes have diabetic peripheral neuropathy. According to this study, the prevalence of diabetic peripheral neuropathy in Ethiopia is considerably high. This evidence suggests that attention should be given to patients with diabetes in monitoring patients' blood glucose.
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Affiliation(s)
- Degena Bahrey Tadesse
- Department of Adult Health Nursing, School of Nursing, Aksum University, Aksum, Ethiopia
| | | | - Abrha Hailay
- Department of Adult Health Nursing, School of Nursing, Aksum University, Aksum, Ethiopia
| | - Woldu Aberhe
- Department of Adult Health Nursing, School of Nursing, Aksum University, Aksum, Ethiopia
| | - Guesh Mebrahtom
- Department of Adult Health Nursing, School of Nursing, Aksum University, Aksum, Ethiopia
| | - Kidane Zereabruk
- Department of Adult Health Nursing, School of Nursing, Aksum University, Aksum, Ethiopia
| | - Guesh Gebreayezgi
- Department of Epidemiology, School of Public Health, Aksum University, Aksum, Ethiopia
| | - Teklewoini Mariye
- Department of Adult Health Nursing, School of Nursing, Aksum University, Aksum, Ethiopia
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Rippetoe J, Wang H, James SA, Dionne C, Block B, Beckner M. Improvement of Gait after 4 Weeks of Wearable Focal Muscle Vibration Therapy for Individuals with Diabetic Peripheral Neuropathy. J Clin Med 2020; 9:E3767. [PMID: 33266464 PMCID: PMC7700661 DOI: 10.3390/jcm9113767] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 11/03/2020] [Accepted: 11/21/2020] [Indexed: 02/06/2023] Open
Abstract
People with diabetic peripheral neuropathy (DPN) experience lower quality of life caused by associated balance, posture, and gait impairments. While focal muscle vibration (FMV) has been associated with improvements in gait performance in individuals with neurological disorders, little is known about its effectiveness in patients with DPN. The purpose of this study was to investigate the effect of FMV on gait outcomes in patients with DPN. The authors randomized 23 participants into three FMV intervention groups depending upon the delivery of vibration. Participants applied wearable FMV to the bilateral quadriceps, gastrocnemius, and tibialis anterior, 10 min per muscle, three times per week over a four-week period. Spatiotemporal, kinematic, and kinetic gait parameters at baseline and post-intervention were calculated and analyzed. Gait speed, cadence, stride time, left and right stance time, duration of double limb support, and left and right knee flexor moments significantly improved after four weeks of FMV. Trends toward significant improvements were noted in maximum left and right knee flexion. Results indicate that FMV therapy was associated with improvements in gait parameters in individuals with DPN, warranting expanded study of FMV therapy for long-term gait performance improvement in these individuals.
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Affiliation(s)
- Josiah Rippetoe
- Department of Rehabilitation Sciences, College of Allied Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (J.R.); (S.A.J.); (C.D.); (B.B.); (M.B.)
| | - Hongwu Wang
- Department of Rehabilitation Sciences, College of Allied Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (J.R.); (S.A.J.); (C.D.); (B.B.); (M.B.)
- Peggy and Charles Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK 73019, USA
| | - Shirley A. James
- Department of Rehabilitation Sciences, College of Allied Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (J.R.); (S.A.J.); (C.D.); (B.B.); (M.B.)
| | - Carol Dionne
- Department of Rehabilitation Sciences, College of Allied Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (J.R.); (S.A.J.); (C.D.); (B.B.); (M.B.)
| | - Bethany Block
- Department of Rehabilitation Sciences, College of Allied Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (J.R.); (S.A.J.); (C.D.); (B.B.); (M.B.)
| | - Matthew Beckner
- Department of Rehabilitation Sciences, College of Allied Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (J.R.); (S.A.J.); (C.D.); (B.B.); (M.B.)
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Maiga Y, Diallo S, Konipo FDN, Sangho O, Sangaré M, Diallo SH, Mahamadou S, Péréon Y, Giumelli B, Coulibaly A, Daou M, Traoré Z, Sow Sylla D, Albakaye M, Guinto CO, Ouologem M, Sissoko AS, Traoré HA, Coulibaly SP, Damier P, Attal N, Nizard J. Diabetic polyneuropathy with/out neuropathic pain in Mali: A cross-sectional study in two reference diabetes treatment centers in Bamako (Mali), Western Africa. PLoS One 2020; 15:e0241387. [PMID: 33166296 PMCID: PMC7652324 DOI: 10.1371/journal.pone.0241387] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Accepted: 10/13/2020] [Indexed: 11/18/2022] Open
Abstract
INTRODUCTION Diabetic polyneuropathy (DPN) with or without neuropathic pain is a frequent complication of diabetes. This work aimed to determine the prevalence of diabetic polyneuropathy, to describe its epidemiological aspects, and to analyze the therapeutic itinerary of patients with DPN. METHODS This was a cross-sectional, descriptive study performed synchronously over six months at two major follow-up sites for patients with diabetes in Mali. DPN was diagnosed based on the Michigan Neuropathy Screening Instrument (MNSI). The neuropathic nature of the pain and the quality of life of patients were evaluated by the DN4 and the ED-5D scale, respectively. We used three (3) different questionnaires to collect data from patients (one at inclusion and another during the follow-up consultation) and from the caregivers of patients with DPN. RESULTS We included 252 patients with diabetes, and DPN was found to have a healthcare facility-based prevalence of 69.8% (176/252). The sex ratio was approximately three females for every male patient. The patients were mostly 31 to 60 years of age, 83% had type 2 diabetes, and 86.9% had neuropathic pain Approximately half of the patients (48.3%) had autonomic neuropathy and they reported moderate to intense pain, which was mainly described as a burning sensation. The patients exhibited impaired exteroceptive and proprioceptive sensations in 51.7% of cases. The patients smoked tobacco in 3.4% of cases, while 36.6% of the patients were obese and had dyslipidemia. The caregivers clearly indicated that appropriate medications were not readily accessible or available for their patients with DPN. CONCLUSION The healthcare facility-based prevalence of DPN with or without neuropathic pain was high in our cohort. These inexpensive and easy-to-use tools (MNSI, DN4) can be used to adequately diagnose DPN in the African context. In Mali, screening and early treatment of patients at risk of DPN should allow for a reduction of the burden of the disease, while caregivers need to be adequately trained to manage DPN.
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Affiliation(s)
- Youssoufa Maiga
- Faculty of Medicine, University of Technical Sciences and Technologies, Bamako, Mali
- Department of Neurology, Gabriel Touré Teaching Hospital, Bamako, Mali
- Laboratory of Therapeutics (EA3826), Faculty of Medicine of Nantes, University of Nantes, Nantes, France
| | - Salimata Diallo
- Department of Neurology, Gabriel Touré Teaching Hospital, Bamako, Mali
| | | | - Oumar Sangho
- Faculty of Medicine, University of Technical Sciences and Technologies, Bamako, Mali
| | - Modibo Sangaré
- Faculty of Medicine, University of Technical Sciences and Technologies, Bamako, Mali
| | - Seybou H. Diallo
- Faculty of Medicine, University of Technical Sciences and Technologies, Bamako, Mali
- Department of Neurology, Gabriel Touré Teaching Hospital, Bamako, Mali
| | | | - Yann Péréon
- Reference Center of Neuromuscular Diseases Atlantique-Occitanie-Caraïbes, Hôtel-Dieu, UHC of Nantes, Nantes, France
| | | | - Awa Coulibaly
- Department of Neurology, Gabriel Touré Teaching Hospital, Bamako, Mali
| | - Mariam Daou
- Department of Neurology, Gabriel Touré Teaching Hospital, Bamako, Mali
| | | | - Djeneba Sow Sylla
- Faculty of Medicine, University of Technical Sciences and Technologies, Bamako, Mali
- Center for Combating Diabetes in Mali (CCD), Bamako, Mali
| | - Mohamed Albakaye
- Department of Neurology, Gabriel Touré Teaching Hospital, Bamako, Mali
| | - Cheick Oumar Guinto
- Faculty of Medicine, University of Technical Sciences and Technologies, Bamako, Mali
| | - Madani Ouologem
- Faculty of Dental Surgery, University of Nantes, Nantes, France
| | - Adama S. Sissoko
- Faculty of Medicine, University of Technical Sciences and Technologies, Bamako, Mali
| | - Hamar A. Traoré
- Faculty of Medicine, University of Technical Sciences and Technologies, Bamako, Mali
| | | | | | - Nadine Attal
- INSERM U 98, CET, CHU Ambroise Paré, 92100 Boulogne-Billancourt, France
| | - Julien Nizard
- Laboratory of Therapeutics (EA3826), Faculty of Medicine of Nantes, University of Nantes, Nantes, France
- Faculty of Medicine, University of Nantes, Nantes, France
- Federal Pain Palliative Care and Support, Laboratory of Therapeutics, Nantes UHC, Nantes, France
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Lapin BR, Pantalone KM, Milinovich A, Morrison S, Schuster A, Boulos F, Johnson K, Thakore NJ. Pain in Patients With Type 2 Diabetes-Related Polyneuropathy Is Associated With Vascular Events and Mortality. J Clin Endocrinol Metab 2020; 105:5861640. [PMID: 32575118 DOI: 10.1210/clinem/dgaa394] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 06/17/2020] [Indexed: 11/19/2022]
Abstract
PURPOSE Type 2 diabetes-related polyneuropathy (DPN) is associated with increased vascular events and mortality, but determinants and outcomes of pain in DPN are poorly understood. We sought to examine the effect of neuropathic pain on vascular events and mortality in patients without DPN, DPN with pain (DPN + P), and DPN without pain (DPN-P). METHODS A retrospective cohort study was conducted within a large health system of adult patients with type 2 diabetes from January 1, 2009 through December 31, 2016. Using an electronic algorithm, patients were classified as no DPN, DPN + P, or DPN-P. Primary outcomes included number of vascular events and time to mortality. Independent associations with DPN + P were evaluated using multivariable negative binomial and Cox proportional hazards regression models, adjusting for demographics, socioeconomic characteristics, and comorbidities. RESULTS Of 43 945 patients with type 2 diabetes (age 64.6 ± 14.0 years; 52.1% female), 13 910 (31.7%) had DPN: 9104 DPN + P (65.4%) vs 4806 DPN-P (34.6%). Vascular events occurred in 4538 (15.1%) of no DPN patients, 2401 (26.4%) DPN + P, and 1006 (20.9%) DPN-P. After adjustment, DPN + P remained a significant predictor of number of vascular events (incidence rate ratio [IRR] = 1.55, 95% CI, 1.29-1.85), whereas no DPN was protective (IRR = 0.70, 95% CI, 0.60-0.82), as compared to DPN-P. Compared to DPN-P, DPN + P was also a significant predictor of mortality (hazard ratio = 1.42, 95% CI, 1.25-1.61). CONCLUSIONS Our study found a significant association between pain in DPN and an increased risk of vascular events and mortality. This observation warrants longitudinal study of the risk factors and natural history of pain in DPN.
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Affiliation(s)
- Brittany R Lapin
- Center for Outcomes Research and Evaluation, Neurological Institute, Cleveland Clinic, Cleveland, Ohio
- Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
| | - Kevin M Pantalone
- Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, Ohio
| | - Alex Milinovich
- Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
| | - Shannon Morrison
- Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
| | - Andrew Schuster
- Center for Outcomes Research and Evaluation, Neurological Institute, Cleveland Clinic, Cleveland, Ohio
| | - Fernanda Boulos
- Novartis Pharmaceuticals Corporation, East Hanover, New Jersey
| | - Kristen Johnson
- Novartis Pharmaceuticals Corporation, East Hanover, New Jersey
| | - Nimish J Thakore
- Department of Neurology/Neuromuscular Center, Neurological Institute, Cleveland Clinic, Cleveland, Ohio
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50
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Matthew Brennan J, Leon MB, Sheridan P, Boero IJ, Chen Q, Lowenstern A, Thourani V, Vemulapalli S, Thomas K, Wang TY, Peterson ED. Racial Differences in the Use of Aortic Valve Replacement for Treatment of Symptomatic Severe Aortic Valve Stenosis in the Transcatheter Aortic Valve Replacement Era. J Am Heart Assoc 2020; 9:e015879. [PMID: 32777969 PMCID: PMC7660794 DOI: 10.1161/jaha.119.015879] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Accepted: 06/19/2020] [Indexed: 12/11/2022]
Abstract
Background Aortic valve replacement (AVR) is a life-saving treatment for patients with symptomatic severe aortic valve stenosis. We sought to determine whether transcatheter AVR has resulted in a more equitable treatment rate by race in the United States. Methods and Results A total of 32 853 patients with symptomatic severe aortic valve stenosis were retrospectively identified via Optum's deidentified electronic health records database (2007-2017). AVR rates in non-Hispanic Black and White patients were assessed in the year after diagnosis. Multivariate Fine-Gray hazards models were used to evaluate the likelihood of AVR by race, with adjustment for patient factors and the managing cardiologist. Time-trend and 1-year symptomatic severe aortic valve stenosis survival analyses were also performed. From 2011 to 2016, the rate of AVR increased from 20.1% to 37.1%. Overall, Black individuals were less likely than Whites to receive AVR (22.9% versus 31.0%; unadjusted hazard ratio [HR], 0.70; 95% CI, 0.62-0.79; fully adjusted HR, 0.76; 95% CI, 0.67-0.85). Yet, during 2015 to 2016, AVR racial differences were attenuated (29.5% versus 35.2%; adjusted HR, 0.86; 95% CI, 0.74-1.02) because of greater uptake of transcatheter AVR in Blacks than Whites (53.4% of AVRs versus 47.3%; P=0.128). Untreated patients had significantly higher 1-year mortality than those treated (adjusted HR, 0.57; 95% CI, 0.53-0.61), which was consistent by race (interaction P value=0.52). Conclusions Although transcatheter AVR has increased the use of AVR in the United States, treatment rates remain low. Black patients with symptomatic severe aortic valve stenosis were less likely than White patients to receive AVR, yet these differences have recently narrowed.
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Affiliation(s)
| | - Martin B. Leon
- Columbia University Medical Center and New York Presbyterian HospitalNew YorkNY
| | - Paige Sheridan
- Department of Family Medicine and Public HealthUniversity of San DiegoSan DiegoCA
- Boston Consulting GroupBostonMA
| | | | | | | | - Vinod Thourani
- Georgetown University School of MedicineMedstar Heart and Vascular InstituteWashingtonDC
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