Dataset Information

Susceptible and Prognostic Genetic Factors Associated with Diabetic Peripheral Neuropathy: A Comprehensive Literature Review.

ABSTRACT: Type 2 diabetes mellitus (T2D) is a disorder of glucose metabolism. It is a complex process involving the regulation of insulin secretion, insulin sensitivity, gluconeogenesis, and glucose uptake at the cellular level. Diabetic peripheral neuropathy (DPN) is one of the debilitating complications that is present in approximately 50% of diabetic patients. It is the primary cause of diabetes-related hospital admissions and nontraumatic foot amputations. The pathogenesis of diabetic neuropathy is a complex process that involves hyperglycemia-induced oxidative stress and altered polyol metabolism that changes the nerve microvasculature, altered growth factor support, and deregulated lipid metabolism. Recent literature has reported that there are several heterogeneous groups of susceptible genetic loci which clearly contribute to the development of DPN. Several studies have reported that some patients with prediabetes develop neuropathic complications, whereas others demonstrated little evidence of neuropathy even after long-standing diabetes. There is emerging evidence that genetic factors may contribute to the development of DPN. This paper aims to provide an up-to-date review of the susceptible and prognostic genetic factors associated with DPN. An extensive survey of the scientific literature published in PubMed using the search terms "Diabetic peripheral neuropathy/genetics" and "genome-wide association study" was carried out, and the most recent and relevant literature were included in this review.

SUBMITTER: Prabodha LBL

PROVIDER: S-EPMC5875044 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Susceptible and Prognostic Genetic Factors Associated with Diabetic Peripheral Neuropathy: A Comprehensive Literature Review.

Prabodha L B L LBL Sirisena N D ND Dissanayake V H W VHW

International journal of endocrinology 20180315

Type 2 diabetes mellitus (T2D) is a disorder of glucose metabolism. It is a complex process involving the regulation of insulin secretion, insulin sensitivity, gluconeogenesis, and glucose uptake at the cellular level. Diabetic peripheral neuropathy (DPN) is one of the debilitating complications that is present in approximately 50% of diabetic patients. It is the primary cause of diabetes-related hospital admissions and nontraumatic foot amputations. The pathogenesis of diabetic neuropathy is a ...[more]

PMID: 29736170

Similar Datasets

Project description:Commonly used chemotherapeutic agents in oncology/hematology practice, causing toxic peripheral neuropathy, include taxanes, platinum compounds, vinca alkaloids, proteasome inhibitors, and antiangiogenic/immunomodulatory agents. This review paper intends to put together and discuss the spectrum of chemotherapy-induced peripheral neuropathy (CIPN) characteristics so as to highlight areas of future research to pursue on the topic. Current knowledge shows that the pathogenesis of CIPN still remains elusive, mostly because there are several sites of involvement in the peripheral nervous system. In any case, it is acknowledged that the dorsal root ganglia of the primary sensory neurons are the most common neural targets of CIPN. Both the incidence and severity of CIPN are clinically under- and misreported, and it has been demonstrated that scoring CIPN with common toxicity scales is associated with significant inter-observer variability. Only a proportion of chemotherapy-treated patients develop treatment-emergent and persistent CIPN, and to date it has been impossible to predict high-and low-risk subjects even within groups who receive the same drug regimen. This issue has recently been investigated in the context of pharmacogenetic analyses, but these studies have not implemented a proper methodological approach and their results are inconsistent and not really clinically relevant. As such, a stringent approach has to be implemented to validate that information. Another open issue is that, at present, there is insufficient evidence to support the use of any of the already tested chemoprotective agents to prevent or limit CIPN. The results of comprehensive interventions, including clinical, neurophysiological, and pharmacogenetic approaches, are expected to produce a consistent advantage for both doctors and patients and thus allow the registration and analysis of reliable data on the true characteristics of CIPN, eventually leading to potential preventive and therapeutic interventions.

Project description:PurposePreoperative diagnosis of pituicytomas is difficult, and management and prognostic factors remain ambiguous. The purpose of this study was to elucidate the radiological characteristics of pituicytoma, to assess the risk factors affecting tumor progression, and to propose the optimal treatment regimen based on comprehensive analysis.MethodsWe reviewed the clinical data of 22 patients with pituicytoma confirmed pathologically in our institution. In addition, 93 cases of pituicytoma in the previous literature were recruited. The individual data of 115 patients were analyzed to evaluate the adverse factors affecting pituicytoma progression.ResultsIn the combined cohort, 3 of 61 patients who underwent gross-total resection (GTR) developed recurrence (4.9%); of the 54 patients who received non-GTR, 19 progressed (35.2%). Univariate and multivariate Cox regression analysis verified male gender (HR 2.855, 95% CI 1.008-8.089; p = 0.048), TS (transsphenoidal surgery; HR 3.559, 95% CI 1.015-12.476; p = 0.047), and non-GTR (HR 4.388, 95%CI 1.240-15.521; p = 0.022) were independent unfavorable factors for pituicytoma progression. A multivariate logistic regression model verified that tumor diameter ≥ 1.85 cm (OR 4.859, 95% CI 1.335-17.691; p = 0.016) was independent adverse factors for GTR. Compared with TS, OT (open transcranial) is more likely to have postoperative complications (OR 3.185, 95% CI 1.020-9.944; p = 0.046), especially vision deterioration (OR 37.267, 95% CI 4.486-309.595; p = 0.001).ConclusionBased on our findings, GTR was advocated as an optimal treatment for pituicytomas. However, in order to avoid damage to important structures, partial resection is acceptable. After that, adjuvant radiotherapy is recommended for male patients with high Ki-67 index, and the remaining patients can be followed up closely. When the tumor recurs or progresses, it is recommended to re-operate and remove the lesion completely as far as possible. If GTR is still not possible, postoperative radiotherapy for the residual tumor is recommended.

Project description:BackgroundCurrently, diabetic peripheral neuropathy (DPN) is one of the most severe complications of diabetes mellitus (DM). Despite the seriousness of this problem, limited evidence is available on the prevalence of diabetic peripheral neuropathy among patients with diabetes mellitus in Ethiopia. In Ethiopia, there were no updated studies that estimate the national prevalence of DPN. Hence, this systematic review and meta-analysis provided a national prevalence of diabetic peripheral neuropathy among patients with diabetes mellitus in Ethiopia.MethodsThis study was submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO) in March 2020 and accepted with the registration number CRD42020173831. Different database searching engines were searched online to retrieve related articles, including PubMed, Scopus, Google Scholar, African Journals Online, World Health Organization (WHO) Afro Library, and Cochrane Review. The reviewers used the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guideline in the reviewing process. In this systematic review and meta-analysis, all published and unpublished articles were analyzed. The reviewers used the random effects model to estimate the pooled prevalence of diabetic peripheral neuropathy among diabetes mellitus patients. The reviewers conducted the statistical analysis using the R version 3.5.3 and RStudio version 1.2.5033 software for Windows. The reviewers evaluated the heterogeneity across the included studies by the inconsistency index (I 2). The reviewers examined the publication bias by the funnel plot.ResultsThe search of the databases produced 245 papers. After checking the inclusion and exclusion criteria, 38 articles with 14029 total patients with diabetes mellitus were found suitable for the review. Except for three (retrospective cohort study), all studies were cross-sectional. The overall pooled prevalence of diabetic peripheral neuropathy was 22% (95% CI 18% to 26%). The subgroup analysis of diabetic peripheral neuropathy among patients with diabetes in the different regions was 23% (95% CI 17% to 29%) in Addis Ababa, 27% (95% CI 16% to 38%) in Oromia, 16% (95% CI 14% to 18%) in South nation and nationalities, and 15% (95% CI 6% to 24%) in Amhara.ConclusionsMore than one-fifth of patients with diabetes have diabetic peripheral neuropathy. According to this study, the prevalence of diabetic peripheral neuropathy in Ethiopia is considerably high. This evidence suggests that attention should be given to patients with diabetes in monitoring patients' blood glucose.

Project description:Neurotoxic anticancer drugs, such as platinum-based anticancer drugs, taxanes, vinca alkaloids, and proteasome/angiogenesis inhibitors are responsible for chemotherapy-induced peripheral neuropathy (CIPN). The health consequences of CIPN remain worrying as it is associated with several comorbidities and affects a specific population of patients already impacted by cancer, a strong driver for declines in older adults. The purpose of this review is to present a comprehensive overview of the long-term effects of CIPN in cancer patients and survivors. Pathophysiological mechanisms and risk factors are also presented. Neurotoxic mechanisms leading to CIPNs are not yet fully understood but involve neuronopathy and/or axonopathy, mainly associated with DNA damage, oxidative stress, mitochondria toxicity, and ion channel remodeling in the neurons of the peripheral nervous system. Classical symptoms of CIPNs are peripheral neuropathy with a "stocking and glove" distribution characterized by sensory loss, paresthesia, dysesthesia and numbness, sometimes associated with neuropathic pain in the most serious cases. Several risk factors can promote CIPN as a function of the anticancer drug considered, such as cumulative dose, treatment duration, history of neuropathy, combination of therapies and genetic polymorphisms. CIPNs are frequent in cancer patients with an overall incidence of approximately 38% (possibly up to 90% of patients treated with oxaliplatin). Finally, the long-term reversibility of these CIPNs remain questionable, notably in the case of platinum-based anticancer drugs and taxanes, for which CIPN may last several years after the end of anticancer chemotherapies. These long-term effects are associated with comorbidities such as depression, insomnia, falls and decreases of health-related quality of life in cancer patients and survivors. However, it is noteworthy that these long-term effects remain poorly studied, and only limited data are available such as in the case of bortezomib and thalidomide-induced peripheral neuropathy.

Project description:BackgroundDecreased lean muscle mass in the lower extremity in diabetic peripheral neuropathy (DPN) is thought to contribute to altered joint loading, immobility, and disability. However, the mechanism behind this loss is unknown and could derive from a reduction in size of myofibers (atrophy), destruction of myofibers (degeneration), or both. Degenerative changes require participation of muscle stem (satellite) cells to regenerate lost myofibers and restore lean mass. Determining the degenerative state and residual regenerative capacity of DPN muscle will inform the utility of regeneration-targeted therapeutic strategies.MethodsBiopsies were acquired from 2 muscles in 12 individuals with and without diabetic neuropathy undergoing below-knee amputation surgery. Biopsies were subdivided for histological analysis, transcriptional profiling, and satellite cell isolation and culture.ResultsHistological analysis revealed evidence of ongoing degeneration and regeneration in DPN muscles. Transcriptional profiling supports these findings, indicating significant upregulation of regeneration-related pathways. However, regeneration appeared to be limited in samples exhibiting the most severe structural pathology as only extremely small, immature regenerated myofibers were found. Immunostaining for satellite cells revealed a significant decrease in their relative frequency only in the subset with severe pathology. Similarly, a reduction in fusion in cultured satellite cells in this group suggests impairment in regenerative capacity in severe DPN pathology.ConclusionDPN muscle exhibited features of degeneration with attempted regeneration. In the most severely pathological muscle samples, regeneration appeared to be stymied and our data suggest that this may be partly due to intrinsic dysfunction of the satellite cell pool in addition to extrinsic structural pathology (eg, nerve damage).Clinical relevanceRestoration of DPN muscle function for improved mobility and physical activity is a goal of surgical and rehabilitation clinicians. Identifying myofiber degeneration and compromised regeneration as contributors to dysfunction suggests that adjuvant cell-based therapies may improve clinical outcomes.

Dataset Information

Susceptible and Prognostic Genetic Factors Associated with Diabetic Peripheral Neuropathy: A Comprehensive Literature Review.

Publications

Susceptible and Prognostic Genetic Factors Associated with Diabetic Peripheral Neuropathy: A Comprehensive Literature Review.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure