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Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial.
Didangelos, T, Karlafti, E, Kotzakioulafi, E, Margariti, E, Giannoulaki, P, Batanis, G, Tesfaye, S, Kantartzis, K
Nutrients. 2021;(2)
Abstract
AIM: To investigate the effect of normalizing vitamin B12 (B12) levels with oral B12 (methylcobalamin) 1000 μg/day for one year in patients with diabetic neuropathy (DN). PATIENTS AND METHODS In this prospective, double-blind, placebo-controlled trial, 90 patients with type 2 diabetes on metformin for at least four years and both peripheral and autonomic DN were randomized to an active treatment group (n = 44) receiving B12 and a control group (n = 46) receiving a placebo. All patients had B12 levels less than 400 pmol/L. Subjects underwent measurements of sural nerve conduction velocity (SNCV), sural nerve action potential (amplitude) (SNAP), and vibration perception threshold (VPT), and they performed cardiovascular autonomic reflex tests (CARTs: mean circular resultant (MCR), Valsalva test, postural index, and orthostatic hypotension). Sudomotor function was assessed with the SUDOSCAN that measures electrochemical skin conductance in hands and feet (ESCH and ESCF, respectively). We also used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE, respectively) and questionnaires to evaluate quality of life (QoL) and level of pain (pain score). RESULTS B12 levels increased from 232.0 ± 71.8 at baseline to 776.7 ± 242.3 pmol/L at follow-up, p < 0.0001, in the active group but not in the control group. VPT, MNSIQ, QoL, pain score, SNCV, SNAP, and ESCF significantly improved in the active group (p < 0.001, p = 0.002, p < 0.0001, p < 0.000, p < 0.0001, p < 0.0001, and p = 0.014, respectively), whereas CARTS and MNSIE improved but not significantly. MCR, MNSIQ, SNCV, SNAP, and pain score significantly deteriorated in the control group (p = 0.025, p = 0.017, p = 0.045, p < 0.0001, and p < 0.0001, respectively). CONCLUSIONS The treatment of patients with DN with 1 mg of oral methylcobalamin for twelve months increased plasma B12 levels and improved all neurophysiological parameters, sudomotor function, pain score, and QoL, but it did not improve CARTS and MNSIE.
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A randomized comparative study of methylcobalamin, methylcobalamin plus pregabalin and methylcobalamin plus duloxetine in patients of painful diabetic neuropathy.
Sharma, C, Kaur, I, Singh, H, Grover, IS, Singh, J
Indian journal of pharmacology. 2021;(5):358-363
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Abstract
CONTEXT Diabetic neuropathy affects 10.5%-32.2% of diabetic population posing clinical burden onto society. AIMS We aimed to study the efficacy, safety, and tolerability of methylcobalamin, methylcobalamin plus pregabalin, and methylcobalamin plus duloxetine in patients of painful diabetic neuropathy. SETTINGS AND DESIGN It is a prospective, randomized, open-label, interventional, and parallel-group study done in patients of painful diabetic neuropathy. MATERIALS AND METHODS A total of 100 patients were recruited and randomized to three study groups A, B, and C on methylcobalamin, methylcobalamin and pregabalin, and methylcobalamin and duloxetine, respectively. Patients were assessed at day 0 and 4, 8, and 12 weeks. The tuning fork test, monofilament test, Thermal Sensitivity testing, and Visual Analog Scale (VAS) were used to analyze vibration, pressure, thermal sensitivity, and pain. STATISTICAL ANALYSIS USED The results are expressed as mean ± standard deviation. Appropriate statistical methods were used to calculate P value (<0.05 - significant). RESULTS The increase in number of patients with vibration perception is 11.6%, 37.9%, and 41.4%; pressure sensation is 7.6%, 37.9%, and 37.9%; and thermal sensitivity is 15.4%, 31.1%, and 37.9% in Groups A, B, and C, respectively. The decrease in VAS scores is 0.58 ± 0.14, 3.82 ± 0.05, and 4.17 ± 0.48 in Groups A, B, and C correspondingly. The adverse effects reported in Groups A, B, and C are 0%, 6.9%, and 10.3%, respectively. CONCLUSIONS Group C is more efficacious when compared to Groups A and B while Group B is safer.
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Evaluation of the efficacy of warm salt water foot-bath on patients with painful diabetic peripheral neuropathy: A randomized clinical trial.
Vakilinia, SR, Vaghasloo, MA, Aliasl, F, Mohammadbeigi, A, Bitarafan, B, Etripoor, G, Asghari, M
Complementary therapies in medicine. 2020;:102325
Abstract
OBJECTIVES Pain relief is one of the main goals of treatment in Diabetic peripheral neuropathy (DPN). Abzan(foot- bath) is one of the effective ways to relief various types of pain in Persian Medicine (PM). DESIGN This study is a randomized clinical trial (RCT) conducted on 60 patients of age range within 30 to 70 years, which were randomly divided into three groups. Group A (warm water bath):For one month each night before bedtime, they were asked to sit on a chair with trousers pulled up to about 5 cm above the ankles and both feet immersed in an electrical foot-bath that contained 5 liters of warm tolerable water (between 40 and 45 ° C) for 15 minutes without any massage. In Group B (salt water bath) was added and dissolved 250 grams of powdered mineral salt to their warm water. Other stages were similar to the group A. Group C (control) did not receive any interventions. Patients were evaluated prior to and following the intervention by the Douleur Neuropathique 4 questionnaire (DN4), The McGill Pain questionnaire and The World Health Organization Bref Quality of Life (WHOQOL-BREF) questionnaire. RESULTS Decrease in DN4 score level in the salt warm water group was significant while The McGill questionnaire showed a significant decrease of pain level the same group. CONCLUSIONS Application of a specific Abzan (salt water bath) may significantly decrease the pain of DPN patients.
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Long-term safety and efficacy of mirogabalin in Asian patients with diabetic peripheral neuropathic pain.
Baba, M, Matsui, N, Kuroha, M, Wasaki, Y, Ohwada, S
Journal of diabetes investigation. 2020;(3):693-698
Abstract
AIMS/INTRODUCTION Diabetic peripheral neuropathic pain (DPNP) affects the functionality, mood and sleep patterns of patients with diabetes. Mirogabalin, an α2 δ ligand with a slower dissociation for α2 δ-1 versus α2 δ-2 subunits, showed efficacy and safety in a randomized, double-blind, placebo-controlled, 14-week study in Asian patients with DPNP. This open-label extension study evaluated the long-term safety and efficacy of mirogabalin in Asian patients with DPNP. MATERIAL AND METHODS This 52-week open-label extension study was carried out in Japan, Korea and Taiwan in patients with DPNP. Patients received mirogabalin, initiated at 5 mg twice daily and increased to a flexible maintenance dosage of 10 or 15 mg twice daily. Adverse events were monitored throughout the study. Patients provided a self-assessment of pain using the Short-Form McGill Pain Questionnaire. RESULTS Of the 214 patients who entered the study, 172 (80.4%) completed the extension study. Of 172 patients who completed the study, 149 received the highest dosage of mirogabalin (15 mg twice daily). The most common treatment-emergent adverse events were nasopharyngitis, diabetic retinopathy, peripheral edema, somnolence, diarrhea, increased weight and dizziness. Most treatment-emergent adverse events were mild or moderate in severity. The incidence of treatment-emergent adverse events leading to treatment discontinuation was 13.1%. The visual analog scale and all other Short-Form McGill Pain Questionnaire subscales (sensory score, affective score, total score and present pain intensity) generally decreased over time from baseline until week 52. CONCLUSIONS This extension study showed the safety and efficacy of a long-term flexible dosing regimen of mirogabalin 10 or 15 mg twice daily in patients with DPNP.
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A Randomized, Double-Blind Study of the Effects of a Sustained Release Formulation of Sodium Nitrite (SR-nitrite) on Patients with Diabetic Neuropathy.
Soin, A, Bock, G, Giordano, A, Patel, C, Drachman, D
Pain physician. 2018;(2):179-190
Abstract
BACKGROUND Sodium nitrite has been reported to be effective in reducing chronic peripheral pain. OBJECTIVES To evaluate the safety and efficacy of 40 and 80 mg, BID, of an oral sustained release formulation of sodium nitrite (SR-nitrite) in patients suffering from diabetic neuropathy, and to determine whether SR-nitrite would reduce the frequency of headaches reported previously by subjects receiving the same doses of an immediate release formulation. STUDY DESIGN Phase II, single-center, randomized, double-blind, placebo controlled clinical trial. SETTING The Ohio Pain Clinic and Kettering Medical Center. METHODS Twenty-four patients were randomized to 40 mg or 80 mg SR-nitrite or placebo twice daily for 12 weeks. The primary objective was to determine whether headaches would be reduced using SR-nitrite. The primary efficacy endpoint was the mean difference in the change of the Neuropathic Pain Symptom Inventory (NPSI) pain score from baseline to that reported after 12 weeks of treatment. Secondary endpoints included changes from baseline for the Brief Pain Inventory (BPI) Scale, the RAND 36 questionnaire, Short Form McGill Questionnaire, daily patient reported score for neuropathic pain, changes in HbA1c, PulseOx and quantitative sensory testing. RESULTS The number of subjects reporting adverse events and the number of adverse events did not change with dose. There were no reports of treatment-related headaches. Although no significant differences were identified in patient responses to the questionnaires, a trend was observed. In the NPSI assessment, patients in the 40 mg and 80 mg dose group reported a 12.7% and 22.0% reduction in pain, respectively, compared to an 8.4% reduction by patients in the placebo group. A trend was also observed with the BPI total severity score. However, the 40 mg dosing group reported the greatest reduction in pain using the McGill Pain index and via patient logs of daily pain scores, where the mean of pain scores reported by subjects in the 40 mg group dropped by day 41 and generally stayed lower than the mean of scores reported by subjects in either of the other two groups. Patients in the 80 mg SR-nitrite group had an improvement in both Nerve Sensory Conductance and Nerve Sensory Velocity. No changes were observed in HbA1c levels or PulseOx. LIMITATIONS Small sample size. CONCLUSION Sustained release sodium nitrite prevents the prevalent reports of headaches by patients treated with an immediate release formulation of sodium nitrite. In a previous study of patients with peripheral arterial disease (PAD), 40 mg BID treatment led to a statistically significant reduction in reported pain, similar trends were observed at the end of the trial period for most of the pain questionnaires used in the study. The 80 mg BID treatment had the more pronounced affect on bioactivity (quantitative sensory testing), which was similar to the PAD study, where this dose group had the greatest improvement in FMD {AU: spell out FMD}. The ability to alleviate pain with BID treatment of SR-nitrite offers promise for a new non-addictive, non-sedating treatment of chronic pain and warrants further study. KEY WORDS Diabetes, diabetic neuropathy, neuropathic pain, peripheral neuropathy, sodium nitrite.
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Retinopathy, Neuropathy, and Subsequent Cardiovascular Events in Patients with Type 2 Diabetes and Acute Coronary Syndrome in the ELIXA: The Importance of Disease Duration.
Seferovic, JP, Bentley-Lewis, R, Claggett, B, Diaz, R, Gerstein, HC, Køber, LV, Lawson, FC, Lewis, EF, Maggioni, AP, McMurray, JJV, et al
Journal of diabetes research. 2018;:1631263
Abstract
INTRODUCTION We investigated the association of diabetic retinopathy and neuropathy with increased risk of recurrent cardiovascular (CV) events in 6068 patients with type 2 diabetes mellitus (T2DM) and recent acute coronary syndrome (ACS) enrolled in the Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA). METHODS History of retinopathy and neuropathy as well as duration of T2DM were self-reported at screening. Proportional hazards regression models were used to assess relationships between retinopathy, neuropathy, and recurrent CV events. RESULTS At screening, retinopathy and neuropathy were reported in 10.7% and 17.5% of patients, respectively, while 5.7% reported both. When adjusted for randomized treatment only, both retinopathy and neuropathy were associated with a primary composite outcome (CV death, nonfatal MI, stroke, or hospitalization for unstable angina) (retinopathy: HR 1.44, 95% CI 1.19-1.75; neuropathy: HR 1.33, 95% CI 1.12-1.57), CV composite (CV death, nonfatal MI, stroke, hospitalization for heart failure (HF)) (retinopathy: HR 1.57, 95% CI 1.31-1.88; neuropathy: HR 1.38, 95% CI 1.19-1.62), myocardial infarction (retinopathy: HR 1.38, 95% CI 1.08-1.76; neuropathy: HR 1.26, 95% CI 1.02-1.54), HF hospitalization (retinopathy: HR 2.03, 95% CI 1.48-2.78; neuropathy: HR 1.71, 95% CI 1.30-2.27), and all-cause mortality (retinopathy: HR 1.65, 95% CI 1.28-2.12; neuropathy: HR 1.43, 95% CI 1.14-1.78). When included in the same model, and adjusted for T2DM duration, there were no independent associations of either with CV outcomes, while T2DM duration remained strongly associated with all outcomes. Addition of demographic characteristics and CV risk factors did not further alter these relationships. CONCLUSIONS In patients with T2DM and recent ACS, a history of retinopathy and/or neuropathy and longer T2DM duration could be considered clinical markers for high risk of recurrent CV events. This trial is registered with the ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome), ClinicalTrials.gov registration number NCT01147250.
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Combined treatment of traditional Chinese medicine and western medicine in the treatment of diabetic peripheral neuropathy.
Xu, JY, Gao, HY
Journal of biological regulators and homeostatic agents. 2018;(4):945-949
Abstract
Diabetic peripheral neuropathy (DPN), a common complication of diabetes, has a high morbidity, and currently there is no effective therapy. To investigate the clinical effect of traditional Chinese medicine in combination with Western medicine, 88 patients with early DPN who were admitted to Binzhou City Center Hospital, Shandong, China, between November 2015 and November 2016, were selected as the research subjects and were randomly divided into a control group and an observation. Patients in the control group were treated by conventional Western medicine, while patients in the observation group were treated by traditional Chinese medicine in addition to conventional Western medicine. The clinical effect was compared between the two groups. The results demonstrated that the overall effective rate of the observation group was much higher than that of the control group, and the difference was statistically significant (P less than 0.05). The vibration perception threshold (VPT) of nervus peroneus communis, nervus suralis and posterior tibial nerve of the two groups significantly declined after treatment (P less than 0.05), however, the decreae in the observation group was more obvious (P less than 0.05). The improvement of glycosylated hemoglobin (HbAlc) and blood glucose of the observation group was superior to that of the control group, and the difference had statistical significance (P less than 0.05). In conclusion, traditional Chinese medicine in combination with Western medicine has a remarkable effect in the treatment of DPN and can effectively relieve vital signs and clinical symptoms of patients and significantly improve nerve conduction velocity. The therapy is worth clinical application and promotion.
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Effect of lifestyle interventions on diabetic peripheral neuropathy in patients with type 2 diabetes, result of a randomized clinical trial.
Ghavami, H, Radfar, M, Soheily, S, Shamsi, SA, Khalkhali, HR
Agri : Agri (Algoloji) Dernegi'nin Yayin organidir = The journal of the Turkish Society of Algology. 2018;(4):165-170
Abstract
OBJECTIVES Diabetic peripheral neuropathy (DPN) is the most common and troublesome complication of diabetes leading to great morbidity and resulting in a huge economic burden for diabetes care. Over half of people with diabetes develop neuropathy. Also, DPN is a major cause of reduced quality of life due to pain, sensory loss, gait instability, fall-related injury, and foot ulceration and amputation. The aim of this study was evaluating the effects of lifestyle interventions on diabetic neuropathy severity in diabetes type 2 outpatients. METHODS This clinical trial conducted on 74 patients with DPN that divided with random allocation into intervention or control group. The lifestyle interventions applied in the intervention group beginning four educational sessions on lifestyle that emphasize strategies for lowering blood sugar, increasing physical activity, promoting weight loss, prudent diet, and foot caring. Each session was lasted for1.5 hour. Then patients followed for 12 weeks. During this period, they received counseling on mentioned lifestyle interventions. DPN severity in both groups measured using modified Toronto Clinical Neuropathy Score (mTCNS) at the beginning of study and at the end of counseling for 12 weeks. RESULTS Comparing differences of mean of DNP severity before and after lifestyle intervention between two groups of study, there was a significant difference (p<0.001). DNP severity in control group had not any change or it increased in some participants, but DNP decreased in intervention group, after applying lifestyle intervention. CONCLUSION Lifestyle interventions can contribute to reducing DPN severity, and consequently decreasing neuropathic pain.
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Effects of alprostadil combined with calcium dobesilate in patients with diabetic peripheral neuropathy.
Han, K, Liu, C, Shi, X, Rao, X
Neuro endocrinology letters. 2018;(2):143-147
Abstract
OBJECTIVE To observe the clinical curative effects of alprostadil combined with calcium dobesilate in type 2 diabetes patients with peripheral neuropathy. METHODS We randomly divided 120 type 2 diabetes patients with diabetic peripheral neuropathy into two groups. The treatment group was prescribed alprostadil (10 μg, once daily) and oral calcium dobesilate (0.5 g, 3 times daily), and the control group was prescribed alprostadil (10 μg, once daily) for a total treatment duration of 2 weeks. The Michigan Diabetic Neuropathy Score (MDNS) and the Michigan Neuropathy Screening Instrument (MNSI) were used to evaluate differences between the two groups before and after treatment. RESULTS Following 2 weeks of treatment, the total effective rate in the treatment group was significantly better than that of the control group (p<0.05) and the MDNS and MNSI scores in the treatment group were significantly lower than those in the control group (p<0.05 or p<0.01). CONCLUSION Combined alprostadil and calcium dobesilate treatment for type 2 diabetic peripheral neuropathy showed good clinical efficacy and an improved curative effect than single alprostadil treatment.
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Efficacy of the Nav1.7 blocker PF-05089771 in a randomised, placebo-controlled, double-blind clinical study in subjects with painful diabetic peripheral neuropathy.
McDonnell, A, Collins, S, Ali, Z, Iavarone, L, Surujbally, R, Kirby, S, Butt, RP
Pain. 2018;(8):1465-1476
Abstract
The effect of PF-05089771, a selective, peripherally restricted Nav1.7 sodium channel blocker on pain due to diabetic peripheral neuropathy was investigated in a randomised, placebo and active-controlled parallel group clinical trial (NCT02215252). A 1-week placebo-run in the period was followed by a 4-week treatment period and a 1-week placebo run-out/taper-down period. Single-blind placebo was administered throughout run-in and run-out periods. Subjects were randomised to receive either PF-05089771 150 mg twice daily, pregabalin 150 mg twice daily, or placebo during the 4-week treatment period. One hundred thirty-five subjects were randomised. The primary endpoint was the average pain score derived from subjects' Numerical Rating Scale scores over the past 7 days of week 4 of the double-blind treatment period. Predefined efficacy criteria for the trial were the effect of PF-05089771 being >0.5 units better than placebo at interim analysis after completion of the first part of the study. Although a trend for a reduction in the weekly average pain score in the PF-05089771 treatment group was observed, this was not statistically significant when compared with placebo at week 4, with a mean posterior difference of -0.41 (90% credible interval: -1.00 to 0.17). The effect of PF-05089771 was smaller than that seen with pregabalin, which was statistically significant when compared with placebo at week 4, with a mean posterior difference of -0.53 (90% credible interval: -0.91 to -0.20). As predefined efficacy criteria were not met, the study did not proceed to the second part. PF-05089771 was well tolerated. Possible reasons for the modest efficacy observed with PF-05089771 are discussed.