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Therapeutic Potential of Ursolic Acid in Cancer and Diabetic Neuropathy Diseases.
Alam, M, Ali, S, Ahmed, S, Elasbali, AM, Adnan, M, Islam, A, Hassan, MI, Yadav, DK
International journal of molecular sciences. 2021;(22)
Abstract
Ursolic acid (UA) is a pentacyclic triterpenoid frequently found in medicinal herbs and plants, having numerous pharmacological effects. UA and its analogs treat multiple diseases, including cancer, diabetic neuropathy, and inflammatory diseases. UA inhibits cancer proliferation, metastasis, angiogenesis, and induced cell death, scavenging free radicals and triggering numerous anti- and pro-apoptotic proteins. The biochemistry of UA has been examined broadly based on the literature, with alterations frequently having been prepared on positions C-3 (hydroxyl), C12-C13 (double bonds), and C-28 (carboxylic acid), leading to several UA derivatives with increased potency, bioavailability and water solubility. UA could be used as a protective agent to counter neural dysfunction via anti-oxidant and anti-inflammatory effects. It is a potential therapeutic drug implicated in the treatment of cancer and diabetic complications diseases provide novel machinery to the anti-inflammatory properties of UA. The pharmacological efficiency of UA is exhibited by the therapeutic theory of one-drug → several targets → one/multiple diseases. Hence, UA shows promising therapeutic potential for cancer and diabetic neuropathy diseases. This review aims to discuss mechanistic insights into promising beneficial effects of UA. We further explained the pharmacological aspects, clinical trials, and potential limitations of UA for the management of cancer and diabetic neuropathy diseases.
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B vitamins as a treatment for diabetic pain and neuropathy.
Karaganis, S, Song, XJ
Journal of clinical pharmacy and therapeutics. 2021;(5):1199-1212
Abstract
WHAT IS KNOWN AND OBJECTIVE B vitamin therapy is a common treatment for diabetic pain and neuropathy, yet its use remains controversial in patients lacking B vitamin deficiencies. The aim of this review was to summarize the current evidence for the efficacy of B vitamin therapy in diabetic patients with neuropathy. COMMENT We screened the English literature for clinical studies evaluating B vitamins as a therapy for pain and neuropathy in diabetic patients. We selected 43 relevant studies for qualitative analysis based on our selection criteria. Our survey of the literature revealed substantive heterogeneity with respect to efficacies of reported outcomes, as well as study design. Most beneficial outcomes were reported against baseline measures, with few positive comparisons against placebo. This highlights the need for larger, placebo-controlled studies. WHAT IS NEW AND CONCLUSION B vitamins should be considered a plausible therapy for diabetic neuropathy, but its overall efficacy remains uncertain and requires further study.
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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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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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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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6.
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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Plant- and Nutraceutical-based Approach for the Management of Diabetes and its Neurological Complications: A Narrative Review.
Öztürk, Y, Öztürk, N
Current pharmaceutical design. 2019;(33):3536-3549
Abstract
Diabetes is an important metabolic disease affecting many organs and systems in the body. The nervous system is one of the body systems affected by diabetes and neuropathic complications are troublesome in diabetic patients with many consequences. As diabetes has deleterious influences almost on bodily systems, an integrative approach seems to be necessary accepting the body as a whole and integrating body systems with lifestyle and living environment. Like some traditional health systems such as Ayurveda, integrative approach includes additional modalities to overcome both diabetes and diabetic complications. In general, these modalities consist of nutraceuticals and plant products. Prebiotics and probiotics are two types of nutraceuticals having active ingredients, such as antioxidants, nutrient factors, microorganisms, etc. Many plants are indicated for the cure of diabetes. All of these may be employed in the prevention and in the non-pharmacological management of mildto- moderate diabetes. Severe diabetes should require appropriate drug selection. Being complementary, prebiotics, probiotics, plants and exercise may be additive for the drug therapy of diabetes. Similarly, there are complementary approaches to prevent and cure neurological and/or behavioral manifestations of diabetes, which may be included in therapy and prevention plans. A scheme is given for the prevention and therapy of comorbid depression, which is one of the most common behavioral complications of diabetes. Within this scheme, the main criterion for the selection of modalities is the severity of diseases, so that personalized management may be developed for diabetic patients using prebiotics and probiotics in their diets, plants and drugs avoiding possible interactions.
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Alpha lipoic acid combined with epalrestat: a therapeutic option for patients with diabetic peripheral neuropathy.
Wang, X, Lin, H, Xu, S, Jin, Y, Zhang, R
Drug design, development and therapy. 2018;:2827-2840
Abstract
BACKGROUND Alpha lipoic acid (ALA), a type of antioxidant, is used in combination with epalrestat in the treatment of diabetic peripheral neuropathy (DPN). However, whether combined treatment is superior to epalrestat monotherapy is controversial. METHODS We conducted a systematic search of PubMed, Cochrane Library and Chinese databases to identify all randomized controlled trials (RCTs) up to October 31, 2017. Data were extracted to evaluate methodological quality and analyzed using Review Manager 5.3.0 software. RESULTS Twelve studies were included. Compared to epalrestat monotherapy, ALA 600 mg/d once a day (qd) combined with epalrestat 50 mg three times a day (tid) augmented the total effectiveness rate (14 days - risk ratio [RR]: 1.40, 95% CI: 1.16-1.69, P=0.0005; 28 days - RR: 1.48, 95% CI: 1.27-1.72, P<0.00001); at the same, it could improve the median motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV), peroneal MNCV, and SNCV after 14, 21, and 28 days of treatment and could reduce the Toronto Clinical Scoring System (TCSS) (weighted mean difference [WMD]: -1.60, 95% CI: (-2.91, -0.29), P=0.02) and Total Symptom Score (TSS) (WMD: -0.93, 95% CI: -1.27, -0.60, P<0.00001) after 21 days of treatment. The treatment strategy of ALA 300 mg/d qd combined with epalrestat 50 mg tid had the same effects in regard to the total effectiveness rate (RR: 1.37, 95% CI: 1.18-1.59, P<0.0001), median MNCV (WMD: 6.12, 95% CI: 5.04, 7.20, P=0.00001), median SNCV (WMD: 6.70, 95% CI: 5.75, 7.65, P=0.00001), peroneal MNCV (WMD: 6.68, 95% CI: 5.82, 7.55, P=0.00001), and peroneal SNCV (WMD: 4.27, 95% CI: 3.34, 5.20, P=0.00001) after 28 days of treatment. CONCLUSION ALA combined with epalrestat is an effective option for DPN patients. Future large-sample RCTs should be conducted to further confirm this finding.
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Effects of acetyl-L-carnitine in diabetic neuropathy and other geriatric disorders.
Sergi, G, Pizzato, S, Piovesan, F, Trevisan, C, Veronese, N, Manzato, E
Aging clinical and experimental research. 2018;(2):133-138
Abstract
A long history of diabetes mellitus and increasing age are associated with the onset of diabetic neuropathy, a painful and highly disabling complication with a prevalence peaking at 50% among elderly diabetic patients. Acetyl-L-carnitine (ALC) is a molecule derived from the acetylation of carnitine in the mitochondria that has an essential role in energy production. It has recently been proposed as a therapy to improve the symptoms of diabetic neuropathy. ALC is widely distributed in mammalian tissues, including the brain, blood-brain barrier, brain neurons, and astrocytes. Aside from its metabolic activity, ALC has demonstrated cytoprotective, antioxidant, and antiapoptotic effects in the nervous system. It exerts an analgesic action by reducing the concentration of glutamate in the synapses. It facilitates nerve regeneration and damage repair after primary trauma: its positive effects on metabolism promote the synthesis, fluidity, and functionality of neuronal membranes, increase protein synthesis, and improve the axonal transport of neurofilament proteins and tubulin. It also amplifies nerve growth factor responsiveness, an effect that is believed to enhance overall neurite growth. ALC has been proposed for the treatment of various neurological and psychiatric diseases, such as mood disorders and depression, dementias, Alzheimer's disease, and Parkinson's disease, because synaptic energy states and mitochondrial dysfunction are core factors in their pathogenesis.
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10.
Prostaglandin E1 plus methylcobalamin combination therapy versus prostaglandin E1 monotherapy for patients with diabetic peripheral neuropathy: A meta-analysis of randomized controlled trials.
Jiang, DQ, Zhao, SH, Li, MX, Jiang, LL, Wang, Y, Wang, Y
Medicine. 2018;(44):e13020
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Abstract
BACKGROUND Prostaglandin E1 (P) or methylcobalamin (M) treatment has been suggested as a therapeutic approach for diabetic peripheral neuropathy (DPN) in many clinical trial reports. However, the combined effects of 2 drugs still remain dubious. OBJECTIVE The aim of this report was to evaluate the efficacy of M plus P (M + P) for the treatment of DPN compared with that of P monotherapy, in order to provide a reference resource for rational drug use. METHODS Randomized controlled trials (RCTs) of M + P for DPN published up to September 2017 were searched. Risk ratio (RR), mean difference (MD), and 95% confidence interval (CI) were calculated and heterogeneity was assessed with the I test. Subgroup and sensitivity analyses were also performed. The outcomes measured were as follows: the clinical efficacy, median motor nerve conduction velocities (MNCV), median sensory nerve conduction velocity (SNCV), peroneal MNCV, peroneal SNCV, and adverse effects. RESULTS Sixteen RCTs with 1136 participants were included. Clinical efficacy of M + P combination therapy was significantly better than P monotherapy (fifteen trials; RR 1.25, 95% CI 1.18-1.32, P < .00001, I = 27%). Compared with P monotherapy, the pooled effects of M + P combination therapy on nerve conduction velocity were (MD 6.29, 95% CI 4.63-7.94, P < .00001, I = 90%) for median MNCV, (MD 5.68, 95% CI 3.53-7.83, P < .00001, I = 94%) for median SNCV, (MD 5.36, 95% CI 3.86-6.87, P < .00001, I = 92%) for peroneal MNCV, (MD 4.62, 95% CI 3.48-5.75, P < .00001, I = 86%) for peroneal SNCV. There were no serious adverse events associated with drug intervention. CONCLUSIONS M + P combination therapy was superior to P monotherapy for improvement of neuropathic symptoms and NCVs in DPN patients. Moreover, no serious adverse events occur in combination therapy.