Diabetic neuropathy in children and adolescents with type 1 diabetes mellitus: Diagnosis, pathogenesis, and associated genetic markers

Kallinikou, Dimitra; Soldatou, Alexandra; Tsentidis, Charalampos; Louraki, Maria; Kanaka‐Gantenbein, Christina; Kanavakis, Emmanouil; Karavanaki, Kyriaki

doi:10.1002/dmrr.3178

Cited by 37 publications

(36 citation statements)

References 176 publications

(194 reference statements)

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“…VEGFA contributes significantly in the pathogenesis of DN, and overexpression will promote the proliferation of microvascular endothelial cells and aggravate the occurrence of vascular disease. The research suggested that VEGFA could serve as biomarkers to identify the progression of DN and had higher expression in the plasma and urine of DN patients [34]. In addition, after treatment with medicine, not only FBG and Scr levels were decreased but also VEGF, HIF-1α, and TGF-β1 mRNA expression was downregulated in DN mice [35].…”

Section: Journal Of Diabetes Researchmentioning

confidence: 99%

Uncovering the Mechanism of Astragalus membranaceus in the Treatment of Diabetic Nephropathy Based on Network Pharmacology

Guo

Dai

Gao

et al. 2020

Journal of Diabetes Research

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Background. Diabetic nephropathy (DN), characterized by hyperglycemia, hypertension, proteinuria, and edema, is a unique microvascular complication of diabetes. Traditional Chinese medicine (TCM) Astragalus membranaceus (AM) has been widely used for DN in China while the pharmacological mechanisms are still unclear. This work is aimed at undertaking a network pharmacology analysis to reveal the mechanism of the effects of AM in DN. Materials and Methods. In this study, chemical constituents of AM were obtained via Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and the potential targets of AM were identified using the Therapeutic Target Database (TTD). DisGeNET and GeneCards databases were used to collect DN-related target genes. DN-AM common target protein interaction network was established by using the STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to further explore the DN mechanism and therapeutic effect of AM. The network diagrams of the active component-action target and protein-protein interaction (PPI) networks were constructed using Cytoscape software. Results. A total of 16 active ingredients contained and 78 putative identified target genes were screened from AM, of which 42 overlapped with the targets of DN and were considered potential therapeutic targets. The analysis of the network results showed that the AM activity of component quercetin, formononetin, calycosin, 7-O-methylisomucronulatol, and quercetin have a good binding activity with top ten screened targets, such as VEGFA, TNF, IL-6, MAPK, CCL3, NOS3, PTGS2, IL-1β, JUN, and EGFR. GO and KEGG analyses revealed that these targets were associated with inflammatory response, angiogenesis, oxidative stress reaction, rheumatoid arthritis, and other biological process. Conclusions. This study demonstrated the multicomponent, multitarget, and multichannel characteristics of AM, which provided a novel approach for further research of the mechanism of AM in the treatment of DN.

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Section: Journal Of Diabetes Researchmentioning

confidence: 99%

Uncovering the Mechanism of Astragalus membranaceus in the Treatment of Diabetic Nephropathy Based on Network Pharmacology

Guo

Dai

Gao

et al. 2020

Journal of Diabetes Research

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“…The hyperglycemia-induced production of pro-inflammatory cytokines affects neurons in the autonomic, central, and peripheral nervous systems. These effects result in enzymatic, metabolic, and microvascular alterations, which would explain why T2DM patients present with diabetic neuropathy as the primary complication of the disease [2,9,15,16]. Overall, the pancreatic cells, adipose tissues, and muscle cells are crucial sites of proinflammatory cytokines production in the presence of obesity.…”

Section: Inflammation and T2dmmentioning

confidence: 99%

Commentary: The Effects of Inflammation, Aging, and Oxidative Stress on the Pathogenesis of Type II Diabetes

Halim

2020

J Health Care and Research

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Type II Diabetes Mellitus (T2DM) is a high-risk metabolic condition associated with high mortality due to hyperglycemia. Many studies have focused on how inflammation, aging, or oxidative stress influences the pathogenesis of T2DM. The functional anomalies of the pancreatic beta cells attribute to insulin resistance which is the primary cause of T2DM manifestations and complications. This is evidenced in polymorphism in the TNF-α gene which inhibits insulin production, metabolism, and utilization during T2DM development. The dysregulation of insulin signaling involves multiple pathways. Various factors such as epigenetics, oxygen radicals, and glucolipotoxicity are implicated in the pathogenesis. Low-grade inflammation mediated by pro-inflammatory cytokines and chemokines such as interleukin-1 attack peripheral tissues and mediates the activation of critical pathways involved in T2DM pathogenesis via transcriptional factors. The core factor resulting in inflammation is hyperglycemia. The result is the release of inflammatory mediators which then affect neurons in the nervous system and alter microvascular and enzymatic pathways to elicit severe complications such as neuropathy. Oxidative stress and inflammation share an intertwined relationship in the pathogenesis of T2DM. High levels of reactive oxygen species increase the level of DNA damage markers and expose pancreatic beta-cell lines to dysregulation through reduced expression of the insulin gene. The link between the interaction of oxidative stress and inflation in the human body increases the level of interleukin-6 which triggers superoxide radicles and oxidative stressors increase which have been shown to affect free fatty acids metabolism inversely Finally, the aspect of cellular senescence in adipocytes and pancreatic beta cells explain why age is a critical factor in T2DM pathogenesis. Overall, the three factors discussed have a crucial role in T2DM disease states, progressions, and complications.

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“…Diabetic neuropathy is often diagnosed too late even though it can develop in children with type 1 diabetes and can be present in subjects with IGT and within 1 year of type 2 diabetes diagnosis . In primary care, the diagnosis of DPN is limited to the annual diabetic review based on a foot examination for “sensory neuropathy” and evaluation of peripheral pulses.…”

Section: Diagnosing Dpn—too Little Too Latementioning

confidence: 99%

Diabetic neuropathy: A focus on small fibres

Malik

2019

Diabetes Metabolism Res

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Diabetic peripheral neuropathy (DPN) is diagnosed too late, which contrasts with our approach for diabetic retinopathy and nephropathy, where incipient disease is detected early enabling timely treatment. The 10‐g monofilament and a foot exam are the commonly used methods for screening diabetic neuropathy, but this primarily identifies moderate to severe diabetic neuropathy. Small fibres are damaged early and are associated with the development of painful diabetic neuropathy, foot ulceration, and Charcot foot. Tests of small fibre damage include thermal thresholds, microneurography, evoked potentials, sudomotor function, laser Doppler flare, skin biopsy, and corneal confocal microscopy. Measures of small fibre damage and repair may be key to the assessment of efficacy in clinical trials of disease modifying therapies for diabetic neuropathy.

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Diabetic neuropathy in children and adolescents with type 1 diabetes mellitus: Diagnosis, pathogenesis, and associated genetic markers

Cited by 37 publications

References 176 publications

Uncovering the Mechanism of Astragalus membranaceus in the Treatment of Diabetic Nephropathy Based on Network Pharmacology

Uncovering the Mechanism of Astragalus membranaceus in the Treatment of Diabetic Nephropathy Based on Network Pharmacology

Commentary: The Effects of Inflammation, Aging, and Oxidative Stress on the Pathogenesis of Type II Diabetes

Diabetic neuropathy: A focus on small fibres

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