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Current Pharmacological Treatment of Painful Diabetic Neuropathy: A Narrative Review.
Ardeleanu, V, Toma, A, Pafili, K, Papanas, N, Motofei, I, Diaconu, CC, Rizzo, M, Stoian, AP
Medicina (Kaunas, Lithuania). 2020;(1)
Abstract
Background and Objectives: Distal symmetrical polyneuropathy (DSPN) is one of the most common chronic complications of diabetes mellitus. Although it is usually characterized by progressive sensory loss, some patients may develop chronic pain. Assessment of DSPN is not difficult, but the biggest challenge is making the correct diagnosis and choosing the right treatment. The treatment of DSPN has three primary objectives: glycemic control, pathogenic mechanisms, and pain management. The aim of this brief narrative review is to summarize the current pharmacological treatment of painful DSPN. It also summarizes knowledge on pathogenesis-oriented therapy, which is generally overlooked in many publications and guidelines. Materials and Methods: The present review reports the relevant information available on DSPN treatment. The search was performed on PubMed, Cochrane, Semantic Scholar, Medline, Scopus, and Cochrane Library databases, including among others the terms "distal symmetrical polyneuropathy", "neuropathic pain treatment", "diabetic neuropathy", "diabetes complications", "glycaemic control", "antidepressants", "opioids", and "anticonvulsants". Results: First-line drugs include antidepressants (selective serotonin reuptake inhibitors and tricyclic antidepressants) and pregabalin. Second- and third-line drugs include opioids and topical analgesics. While potentially effective in the treatment of neuropathic pain, opioids are not considered to be the first choice because of adverse reactions and addiction concerns. Conclusions: DSPN is a common complication in patients with diabetes, and severely affects the quality of life of these patients. Although multiple therapies are available, the guidelines and recommendations regarding the treatment of diabetic neuropathy have failed to offer a unitary consensus, which often hinders the therapeutic options in clinical practice.
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Treatment of diabetic peripheral neuropathy: a review.
Khdour, MR
The Journal of pharmacy and pharmacology. 2020;(7):863-872
Abstract
OBJECTIVES This review surveys current pharmacotherapies available for the treatment of diabetic peripheral neuropathy (DPN), emphasising their mechanisms of action. METHODS A comprehensive literature review focusing on the 'pharmacotherapy and treatment of diabetic peripheral neuropathy' was conducted. The Database of International Pharmaceutical Abstracts, EMBASE, PubMed, OVID, Scopus, Google and Google Scholar were searched, and reference lists of relevant articles were also included. KEY FINDINGS Diabetic peripheral neuropathy is often inadequately treated, and the role of improving glycaemic control specifically in type-2 diabetes remains unclear. It is crucial to explore the mechanisms of action and effectiveness of available therapies. Major international clinical guidelines for the management of DPN recommend several symptomatic treatments. First-line therapies include tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, and anticonvulsants that act on calcium channels. Other therapies include opioids and topical agents such as capsaicin and lidocaine. The objectives of this paper are to review current guidelines for the pharmacological management of DPN and to discuss research relevant to the further development of pharmacological recommendations for the treatment of diabetic neuropathy. SUMMARY Diabetic neuropathy is a highly prevalent, disabling condition, the management of which is associated with significant costs. Evidence supports the use of specific anticonvulsants and antidepressants for pain management in patients with diabetic peripheral neuropathy. All current guidelines advise a personalised approach with a low-dose start that is tailored to the maximum response having the least side effects or adverse events.
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3.
Is there cardiac autonomic neuropathy in prediabetes?
Zilliox, LA, Russell, JW
Autonomic neuroscience : basic & clinical. 2020;:102722
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Abstract
Although there is considerably more data showing an association between type 2 diabetes mellitus (T2DM) and autonomic neuropathy, accumulating evidence indicates that cardiovascular autonomic neuropathy (CAN) is common in persons with impaired glucose tolerance (IGT). Furthermore, CAN may occur early after a metabolic insult and obesity, especially among mean, and seems to play an important role in the early pathogenesis of CAN. Autonomic symptoms are common in subjects with IGT. In addition to defects in CAN, in subjects with IGT, there is impaired sudomotor function and abnormalities of endothelial peripheral vasoreactivity. At the present time, the only interventions that may be effective in preventing or reversing IGT associated autonomic neuropathy are lifestyle improvement. These include a tailored diet and exercise program. Other approaches that may be beneficial include modulation of oxidative stress and improvement of metabolic regulation in subjects with IGT. Interventions are most likely to be effective early in the course of disease and therefore it is extremely important to have early diagnosis of IGT and autonomic neuropathy.
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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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Manual Acupuncture or Combination with Vitamin B to Treat Diabetic Peripheral Neuropathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Jiang, HL, Jia, P, Fan, YH, Li, MD, Cao, CC, Li, Y, Du, YZ
BioMed research international. 2020;:4809125
Abstract
METHODS Randomized controlled trials on manual acupuncture treatment of DPN were retrieved from the Medline, Web of Science, PubMed, Cochrane Library, EMBASE, CNKI, WanFang, and VIP databases. Extracted research data were summarized in the tables, and methodological assessment was performed using the risk-of-bias assessment tool of Cochrane. Meta-analysis was performed by Revman 5.3, Stata 14.0, and TSA 0.9.5.10 Beta software. RESULTS A total of 18 randomized clinical trials (RCTs) were recruited: (1) 11 RCTs were acupuncture alone compared with vitamin B; (2) 7 RCTs were acupuncture combined with vitamin B compared with vitamin B, involving 1200 participants. Acupuncture alone improved clinical efficacy (P < 0.05) and nerve conduction velocity of the four peripheral nerves: peroneal nerve, tibial nerve, median nerve, and ulnar nerve (P < 0.05), but there was no significant difference between the group of acupuncture alone and the group of vitamin B (P = 0.36 > 0.05) in improving median nerve SCV (sensory nerve conduction velocity). Acupuncture combined with vitamin B improved clinical efficacy and nerve conduction velocity of the three peripheral nerves, peroneal nerve, tibial nerve, and median nerve (P < 0.05), and decreased the scores of the Toronto clinical scoring system (TCSS) (P < 0.05). CONCLUSION Acupuncture alone and vitamin B combined with acupuncture are more effective in treating DPN compared to vitamin B. However, more high-quality RCTs on vitamin B combined with acupuncture are required to confirm our results.
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Treatment-Induced Neuropathy of Diabetes (TIND) in Pediatrics: A Case Report and Review of the Literature.
Chandler, E, Brown, M, Wintergerst, K, Doll, E
The Journal of clinical endocrinology and metabolism. 2020;(2)
Abstract
CONTEXT Treatment-induced neuropathy of diabetes (TIND) is a rarely reported but important consideration in patients presenting with an acute onset of neuropathic symptoms following rapid correction of hyperglycemia in diabetes. Although it has been reported in children, the preponderance of literature focuses on adults with TIND. CASE DESCRIPTION We report an 18-year-old male with this condition and his clinical course. We then discuss the proposed pathophysiology of TIND and review the literature. We also provide a standard workup for the diagnosis of TIND. CONCLUSION In both pediatric and adult populations, TIND should be considered in diabetic patients who develop neuropathy acutely following rapid correction of hyperglycemia. Because the pathophysiology of TIND remains poorly understood, there is insufficient information regarding how to target susceptible individuals and prevent the development of TIND.
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Association between Iron Intake and Diabetic Peripheral Neuropathy in Type 2 Diabetes: Significance of Iron Intake and the Ratio between Iron Intake and Polyunsaturated Fatty Acids Intake.
Kim, K, Song, Y, Oh, TJ, Choi, SH, Jang, HC
Nutrients. 2020;(11)
Abstract
We aimed to investigate the association of iron and polyunsaturated fatty acid (PUFA) intake with diabetic peripheral neuropathy (DPN) in individuals with type 2 diabetes. This cross-sectional study included 147 individuals with type 2 diabetes. Dietary intake was assessed using three-day food records. DPN was diagnosed on the basis of a Michigan Neuropathy Screening Instrument-Physical Examination score ≥2.5. Adjusted for total energy intake, iron intake was significantly higher in individuals with DPN than in those without DPN (10.9 ± 4.0 mg vs. 9.9 ± 3.6 mg, p = 0.041). In addition, the iron/PUFA ratio was significantly higher in individuals with DPN (1.4 ± 0.8 vs. 1.1 ± 0.4, p = 0.005). Logistic regression analyses showed that iron intake (odds ratio (OR): 1.152; 95% confidence interval (CI): 1.012, 1.311) and iron/PUFA ratio (OR: 2.283; 95% CI: 1.066, 4.887) were associated with DPN after adjustment for total energy intake, sex, age, body mass index, systolic blood pressure, diabetes duration, estimated glomerular filtration rate, glycated hemoglobin, low-density lipoprotein cholesterol, and smoking. In conclusion, high dietary iron intake and an elevated iron/PUFA ratio were associated with the presence of DPN. The present study suggests the importance of the dietary pattern of iron and PUFA intake in individuals with type 2 diabetes.
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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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Predictive model to identify the risk of losing protective sensibility of the foot in patients with diabetes mellitus.
Chicharro-Luna, E, Pomares-Gómez, FJ, Ortega-Ávila, AB, Marchena-Rodríguez, A, Blanquer-Gregori, JFJ, Navarro-Flores, E
International wound journal. 2020;(1):220-227
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Abstract
Diabetic neuropathy is defined as the presence of symptoms and signs of peripheral nerve dysfunction in diabetics. The aim of this study is to develop a predictive logistic model to identify the risk of losing protective sensitivity in the foot. This descriptive cross-sectional study included 111 patients diagnosed with diabetes mellitus. Participants completed a questionnaire designed to evaluate neuropathic symptoms, and multivariate analysis was subsequently performed to identify an optimal predictive model. The explanatory capacity was evaluated by calculating the R2 coefficient of Nagelkerke. Predictive capacity was evaluated by calculating sensitivity, specificity, and estimation of the area under the receiver operational curve. Protective sensitivity loss was detected in 19.1% of participants. Variables associated by multivariate analysis were: educational level (OR: 31.4, 95% CI: 2.5-383.3, P = .007) and two items from the questionnaire: one related to bleeding and wet socks (OR: 28.3, 95% CI: 3.7-215.9, P = .001) and the other related to electrical sensations (OR: 52.9, 95% CI: 4.3-643.9, P = .002), which were both statistically significant. The predictive model included the variables of age, sex, duration of diabetes, and educational level, and it had a sensitivity of 81.3% and a specificity of 95.5%. This model has a high predictive capacity to identify patients at risk of developing sensory neuropathy.
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Association of non-alcoholic fatty liver disease with microvascular complications of type 2 diabetes.
Afarideh, M, Aryan, Z, Ghajar, A, Ganji, M, Ghaemi, F, Saadat, M, Heidari, B, Mechanick, JI, Esteghamati, A
Primary care diabetes. 2019;(6):505-514
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) affects risks of type 2 diabetes (T2D), diabetes-related complications, and cardiovascular disease in a complex manner. This study is designed to clarify associations of sonographically-detected NAFLD and serum liver enzymes with diabetes-related microvascular complications. METHODS A matched case-contorl study was designed for 440 patients with T2D and at least one of the chronic diabetes-related microvascular complications and 495 age- and gender-matched control patients with T2D. RESULTS Considering pre-existing and newly developed chronic microvascular complications, diabetic peripheral neuropathy was found in 347 out of 935 (37.1%) study patients, diabetic retinopathy in 141/935 (15.1%), and diabetic nephropathy in 103/935 (11.0%). Diagnosis of diabetic retinopathy and diabetic nephropathy were inversely associated with the presence of NAFLD in the crude logistic regressions (OR [95% CI] = 0.18 [0.05-0.63], p value = 0.007; OR [95% CI] = 0.17 [0.04-0.59], p value = 0.011, respectively). The subgroup of NAFLD with elevated liver enzymes had lower odds of having diabetic peripheral neuropathy in the fully adjusted model (OR [95% CI] = 0.34 [0.12-0.98], p value = 0.048). CONCLUSION Diagnosis of NAFLD with or without elevated serum liver enzymes was inversely correlated with certain chronic diabetes microvascular complications. Possible explanations for this counter-intuitive and unexpected finding are discussed and center on reverse-causality, wherein sicker patients may develop beneficial compensatory physiological and behavioral adaptations. Diversity of studied patients, in particular with regards to the ethnic and racial differences among the Western and Asian populations may also partly account for contrasting findings of the relationship between NAFLD and microvascular complications of diabetes.