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1.
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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2.
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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3.
The impact of diabetes on corneal nerve morphology and ocular surface integrity.
Markoulli, M, Flanagan, J, Tummanapalli, SS, Wu, J, Willcox, M
The ocular surface. 2018;(1):45-57
Abstract
Diabetes mellitus is a chronic disease that results from inadequate insulin production or ineffective insulin utilization. It is one of the most common systemic diseases worldwide with increasing prevalence. Diabetes mellitus is associated with premature mortality, macrovascular complications such as cardiovascular disease, and microvascular complications, including nephropathy leading to kidney failure, potentially blinding diabetic retinopathy, and diabetic neuropathy. While the retinal complications of diabetes are well recognized by eye care professionals, the effects on the ocular surface are poorly understood. Recent studies have reported on the association between peripheral neuropathy and corneal neuropathy, showing the latter to be of predictive value for the systemic disease. Corneal neuropathy can lead to loss of corneal sensation and can ultimately result in neurotrophic ulcers and significant visual morbidity. The epithelial fragility and poor wound healing that result from reduced epithelial adhesion to the underlying basement membrane in diabetes, together with corneal neuropathy, are thought to increase the susceptibility to persistent corneal erosions and infection, as well as to increase the risk of post-surgical complications. The aim of this article is to review the impact of diabetes on corneal nerve morphology and ocular surface integrity. Changes in the tear film and ocular surface microbiome are highlighted in discussion of the mechanisms that underpin ocular surface changes that increase the susceptibility to corneal erosion and infection.
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4.
[Alpha-lipoic acid in the treatment of diabetic polyneuropathy].
Chukanova, EI, Chukanova, AS
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2018;(1):103-109
Abstract
The issues of classification, pathogenesis, pathomorphology and treatment of diabetic polyneuropathy (DPN) are addressed. Pathogenetic mechanisms of the action of alpha-lipoic acid in treatment of DPN are justified. The authors present the results of randomized placebo-controlled trials of alpha-lipoic acid that revealed the high clinical efficacy and absence of side-effects even during the long-term treatment.
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5.
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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6.
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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Interventions for Neuropathic Pain: An Overview of Systematic Reviews.
Dosenovic, S, Jelicic Kadic, A, Miljanovic, M, Biocic, M, Boric, K, Cavar, M, Markovina, N, Vucic, K, Puljak, L
Anesthesia and analgesia. 2017;(2):643-652
Abstract
Numerous interventions for neuropathic pain (NeuP) are available, but its treatment remains unsatisfactory. We systematically summarized evidence from systematic reviews (SRs) of randomized controlled trials on interventions for NeuP. Five electronic databases were searched up to March 2015. Study quality was analyzed using A Measurement Tool to Assess Systematic Reviews. The most common interventions in 97 included SRs were pharmacologic (59%) and surgical (15%). The majority of analyzed SRs were of medium quality. More than 50% of conclusions from abstracts on efficacy and approximately 80% on safety were inconclusive. Effective interventions were described for painful diabetic neuropathy (pregabalin, gabapentin, certain tricyclic antidepressants [TCAs], opioids, antidepressants, and anticonvulsants), postherpetic neuralgia (gabapentin, pregabalin, certain TCAs, antidepressants and anticonvulsants, opioids, sodium valproate, topical capsaicin, and lidocaine), lumbar radicular pain (epidural corticosteroids, repetitive transcranial magnetic stimulation [rTMS], and discectomy), cervical radicular pain (rTMS), carpal tunnel syndrome (carpal tunnel release), cubital tunnel syndrome (simple decompression and ulnar nerve transposition), trigeminal neuralgia (carbamazepine, lamotrigine, and pimozide for refractory cases, rTMS), HIV-related neuropathy (topical capsaicin), and central NeuP (certain TCAs, pregabalin, cannabinoids, and rTMS). Evidence about interventions for NeuP is frequently inconclusive or completely lacking. New randomized controlled trials about interventions for NeuP are necessary; they should address safety and use clear diagnostic criteria.
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9.
Advances in the management of diabetic neuropathy.
Várkonyi, T, Körei, A, Putz, Z, Martos, T, Keresztes, K, Lengyel, C, Nyiraty, S, Stirban, A, Jermendy, G, Kempler, P
Minerva medica. 2017;(5):419-437
Abstract
The authors review current advances in the therapy of diabetic neuropathy. The role of glycemic control and management of cardiovascular risk factors in the prevention and treatment of neuropathic complications are discussed. As further options of pathogenetically oriented treatment, recent knowledge on benfotiamine and alpha-lipoic acid is comprehensively reviewed. Alpha-lipoic acid is a powerful antioxidant and clinical trials have proven its efficacy in ameliorating neuropathic signs and symptoms. Benfotiamine acts via the activation of transketolase and thereby inhibits alternative pathways triggered by uncontrolled glucose influx in the cells comprising polyol, hexosamine, protein-kinase-C pathways and formation of advanced glycation end products. Beyond additional forms of causal treatment, choices of symptomatic treatment will be summarized. The latter is mostly represented by the anticonvulsive agents pregabalin and gabapentin as well as duloxetine widely acknowledged as antidepressant. Finally, non-pharmacological therapeutic alternatives are summarized. The authors conclude that combination therapy should be more often suggested to our patients; especially the combination of pathogenetic and symptomatic agents.
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Effect of cilostazol in treating diabetes-associated microvascular complications.
Asal, NJ, Wojciak, KA
Endocrine. 2017;(2):240-244
Abstract
PURPOSE Cilostazol (Pletal), a phosphodiesterase-3 inhibitor, was approved in the United States in 1999 to reduce symptoms of intermittent claudication. Cyclic adenosine monophosphate levels increase from inhibition of phosphodiesterase resulting in anti-platelet, anti-inflammatory, and vasodilatory effects. Diabetes mellitus is a chronic disease that causes endothelial and platelet dysfunction leading to both microvascular and macrovascular complications. This mini-review highlights the emerging evidence suggesting benefits of using cilostazol in treating microvascular complications associated with diabetes mellitus. METHODS A review of literature was conducted using PubMed and Embase databases focusing on cilostazol use in diabetes mellitus. RESULTS Cilostazol demonstrated renoprotective effects in patients with diabetic nephropathy by reducing serum soluble adhesion molecule-1 and monocyte chemoattractant protein-1. Cilostazol's anti-inflammatory actions predictably attenuate glomerular damage from increased leukocyte adherence. Additionally, cilostazol delayed renal dysfunction secondary to type 2 diabetes mellitus as albuminuria was reduced most likely resulting from inhibition of nuclear factor kappa-induced inflammatory and endothelial markers. Cilostazol's anti-inflammatory actions in addition to its vasodilatory actions relieved retinal hypoxia and decreased excessive production of retinal blood vessels suggesting benefit in diabetic retinopathy. Cilostazol did not improve neuropathy symptom scores signifying that it may not be as beneficial in patients with diabetic peripheral neuropathy without diabetic nephropathy or diabetic retinopathy. CONCLUSIONS Cilostazol's pleiotropic effects may be beneficial in patients with type 2 diabetes mellitus and diabetic nephropathy. Additional, larger studies need to be conducted to assess the benefits and risks of using cilostazol as an alternative agent in treating patients with diabetic microvascular complications.