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1.
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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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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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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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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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.
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[Diagnosis of lower limb pain in a diabetic patient].
Philips, JC, Rorive, M, Scheen, AJ
Revue medicale de Liege. 2017;(11):513-518
Abstract
By presenting this clinical case, we aim at discussing the diagnosis between arteriopathy, neuropathy and osteoarticular pathology in a patient with type 2 diabetes who complains of lower limb pain. We emphasize the role of a global medical approach based upon anamnesis and clinical exam, which should contribute to select the most helpful paraclinical investigations.
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Administration of Traditional Chinese Blood Circulation Activating Drugs for Microvascular Complications in Patients with Type 2 Diabetes Mellitus.
He, L, Wang, H, Gu, C, He, X, Zhao, L, Tong, X
Journal of diabetes research. 2016;:1081657
Abstract
Traditional Chinese medicine (TCM) is an important complementary strategy for treating diabetes mellitus (DM) in China. Traditional Chinese blood circulation activating drugs are intended to guide an overall approach to the prevention and treatment of microvascular complications of DM. The core mechanism is related to the protection of the vascular endothelium and the basement membrane. Here, we reviewed the scientific evidence underpinning the use of blood circulation activating drugs to prevent and treat DM-induced microvascular complications, including diabetic nephropathy (DN), diabetic peripheral neuropathy (DPN), and diabetic retinopathy (DR). Furthermore, we summarized the effects and mechanism of TCM on improving blood rheology, inhibiting aggregation of platelet, forming advanced glycation end products (AGEs), regulating oxidative stress, reducing blood fat, and improving lipid metabolism. The paper provides a new theoretical basis for the clinical practice of TCM in the prevention and treatment of DM and its microvascular complications.
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Treating Diabetic Neuropathy: Present Strategies and Emerging Solutions.
Javed, S, Alam, U, Malik, RA
The review of diabetic studies : RDS. 2015;(1-2):63-83
Abstract
Diabetic peripheral neuropathies (DPN) are a heterogeneous group of disorders caused by neuronal dysfunction in patients with diabetes. They have differing clinical courses, distributions, fiber involvement (large or small), and pathophysiology. These complications are associated with increased morbidity, distress, and healthcare costs. Approximately 50% of patients with diabetes develop peripheral neuropathy, and the projected rise in the global burden of diabetes is spurring an increase in neuropathy. Distal symmetrical polyneuropathy (DSPN) with painful diabetic neuropathy, occurring in around 20% of diabetes patients, and diabetic autonomic neuropathy (DAN) are the most common manifestations of DPN. Optimal glucose control represents the only broadly accepted therapeutic option though evidence of its benefit in type 2 diabetes is unclear. A number of symptomatic treatments are recommended in clinical guidelines for the management of painful DPN, including antidepressants such as amitriptyline and duloxetine, the γ-aminobutyric acid analogues gabapentin and pregabalin, opioids, and topical agents such as capsaicin. However, monotherapy is frequently not effective in achieving complete resolution of pain in DPN. There is a growing need for head-to-head studies of different single-drug and combination pharmacotherapies. Due to the ubiquity of autonomic innervation in the body, DAN causes a plethora of symptoms and signs affecting cardiovascular, urogenital, gastrointestinal, pupillomotor, thermoregulatory, and sudomotor systems. The current treatment of DAN is largely symptomatic, and does not correct the underlying autonomic nerve deficit. A number of novel potential candidates, including erythropoietin analogues, angiotensin II receptor type 2 antagonists, and sodium channel blockers are currently being evaluated in phase II clinical trials.
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Acute painful diabetic neuropathy: an uncommon, remittent type of acute distal small fibre neuropathy.
Tran, C, Philippe, J, Ochsner, F, Kuntzer, T, Truffert, A
Swiss medical weekly. 2015;:w14131
Abstract
INTRODUCTION Acute painful diabetic neuropathy (APDN) is a distinctive diabetic polyneuropathy and consists of two subtypes: treatment-induced neuropathy (TIN) and diabetic neuropathic cachexia (DNC). The characteristics of APDN are (1.) the small-fibre involvement, (2.) occurrence paradoxically after short-term achievement of good glycaemia control, (3.) intense pain sensation and (4.) eventual recovery. In the face of current recommendations to achieve quickly glycaemic targets, it appears necessary to recognise and understand this neuropathy. METHODS AND RESULTS Over 2009 to 2012, we reported four cases of APDN. Four patients (three males and one female) were identified and had a mean age at onset of TIN of 47.7 years (±6.99 years). Mean baseline HbA1c was 14.2% (±1.42) and 7.0% (±3.60) after treatment. Mean estimated time to correct HbA1c was 4.5 months (±3.82 months). Three patients presented with a mean time to symptom resolution of 12.7 months (±1.15 months). One patient had an initial normal electroneuromyogram (ENMG) despite the presence of neuropathic symptoms, and a second abnormal ENMG showing axonal and myelin neuropathy. One patient had a peroneal nerve biopsy showing loss of large myelinated fibres as well as unmyelinated fibres, and signs of microangiopathy. CONCLUSIONS According to the current recommendations of promptly achieving glycaemic targets, it appears necessary to recognise and understand this neuropathy. Based on our observations and data from the literature we propose an algorithmic approach for differential diagnosis and therapeutic management of APDN patients.
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Risk Factors and Comorbidities in Diabetic Neuropathy: An Update 2015.
Papanas, N, Ziegler, D
The review of diabetic studies : RDS. 2015;(1-2):48-62
Abstract
Distal symmetric sensorimotor polyneuropathy (DSPN) is the most common neurological manifestation in diabetes. Major risk factors of DSPN include diabetes duration, hyperglycemia, and age, followed by prediabetes, hypertension, dyslipidemia, and obesity. Height, smoking, insulin resistance, hypoinsulinemia, and others represent an additional risk. Importantly, hyperglycemia, hypertension, dyslipidemia, obesity, and smoking are modifiable. Stringent glycemic control has been shown to be effective in type 1, but not to the same extent in type 2 diabetes. Antilipidemic treatment, especially with fenofibrate, and multi-factorial intervention have produced encouraging results, but more experience is necessary. The major comorbidities of DSPN are depression, autonomic neuropathy, peripheral arterial disease, cardiovascular disease, nephropathy, retinopathy, and medial arterial calcification. Knowledge of risk factors and comorbidities has the potential to enrich the therapeutic strategy in clinical practice as part of the overall medical care for patients with neuropathy. This article provides an updated overview of DSPN risk factors and comorbidities.