Importance of Metabolic Memory in the Development of Vascular Complications in Diabetic Patients

Luna, Pastor; Guarner, Verónica; Farías, José María; Hernández-Pacheco, Guadalupe; Martínez, Martín

doi:10.1053/j.jvca.2016.02.008

Cited by 17 publications

(24 citation statements)

References 84 publications

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“…Additional information about the ssGSEA approach is presented in the README tab of Supplemental File 3. This analysis identified increased activity of several pathways linked to epigenetic regulation, which is increasingly understood to drive diabetic complications and explain the clinically recognized phenomenon of metabolic memory 34 . We then searched for pathways whose transcriptional activity was associated with the activity of “DNA methylation” pathway, and use the correlations among them to create a network (Fig.…”

Section: Resultsmentioning

confidence: 99%

Systems Immunology of Diabetes-Tuberculosis Comorbidity Reveals Signatures of Disease Complications

Prada-Medina

Fukutani

Kumar

et al. 2017

Sci Rep

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Comorbid diabetes mellitus (DM) increases tuberculosis (TB) risk and adverse outcomes but the pathological interactions between DM and TB remain incompletely understood. We performed an integrative analysis of whole blood gene expression and plasma analytes, comparing South Indian TB patients with and without DM to diabetic and non-diabetic controls without TB. Luminex assay of plasma cytokines and growth factors delineated a distinct biosignature in comorbid TBDM in this cohort. Transcriptional profiling revealed elements in common with published TB signatures from cohorts that excluded DM. Neutrophil count correlated with the molecular degree of perturbation, especially in TBDM patients. Body mass index and HDL cholesterol were negatively correlated with molecular degree of perturbation. Diabetic complication pathways including several pathways linked to epigenetic reprogramming were activated in TBDM above levels observed with DM alone. Our data provide a rationale for trials of host-directed therapies in TBDM, targeting neutrophilic inflammation and diabetic complication pathways to address the greater morbidity and mortality associated with this increasingly prevalent dual burden of communicable and non-communicable diseases.

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Section: Resultsmentioning

confidence: 99%

Systems Immunology of Diabetes-Tuberculosis Comorbidity Reveals Signatures of Disease Complications

Prada-Medina

Fukutani

Kumar

et al. 2017

Sci Rep

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“…Thus, the phenomenon of metabolic memory or epigenetic memory has been proposed for the aberrant gene expressions even after normalization of blood glucose once a specific period of hyperglycemic exposure had previously occurred [24–27,49]. To contest this disease therefore candidate gene approach is an essentiality to study the pathogenic mechanisms underlying DR [50–52].…”

Section: Diabetic Retinopathymentioning

confidence: 99%

Genetic and epigenetic modifications in the pathogenesis of diabetic retinopathy: a molecular link to regulate gene expression

Pradhan¹,

Upadhyay²,

Tiwari³

et al. 2016

New Front Ophthalmol

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Intensification in the frequency of diabetes and the associated vascular complications has been a root cause of blindness and visual impairment worldwide. One such vascular complication which has been the prominent cause of blindness; retinal vasculature, neuronal and glial abnormalities is diabetic retinopathy (DR), a chronic complicated outcome of Type 1 and Type 2 diabetes. It has also become clear that “genetic” variations in population alone can’t explain the development and progression of diabetes and its complications including DR. DR experiences engagement of foremost mediators of diabetes such as hyperglycemia, oxidant stress, and inflammatory factors that lead to the dysregulation of “epigenetic” mechanisms involving histone acetylation and histone and DNA methylation, chromatin remodeling and expression of a complex set of stress-regulated and disease-associated genes. In addition, both elevated glucose concentration and insulin resistance leave a robust effect on epigenetic reprogramming of the endothelial cells too, since endothelium associated with the eye aids in maintaining the vascular homeostasis. Furthermore, several studies conducted on the disease suggest that the modifications of the epigenome might be the fundamental mechanism(s) for the proposed metabolic memory’ resulting into prolonged gene expression for inflammation and cellular dysfunction even after attaining the glycemic control in diabetics. Henceforth, the present review focuses on the aspects of genetic and epigenetic alterations in genes such as vascular endothelial growth factor and aldose reductase considered being associated with DR. In addition, we discuss briefly the role of the thioredoxin-interacting protein TXNIP, which is strongly induced by high glucose and diabetes, in cellular oxidative stress and mitochondrial dysfunction potentially leading to chromatin remodeling and ocular complications of diabetes. The identification of disease-associated genes and their epigenetic regulations will lead to potential new drugs and gene therapies as well as personalized medicine to prevent or slow down the progression of DR.

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“…There is growing evidence supporting the role of ‘metabolic memory’ in diabetic complications and metabolic memory plays a critical role in the development of vascular complications in diabetic patients [9,10]. Metabolic memory is the phenomenon of diabetic vascular stresses, which can persist after glucose normalization in diabetic patients due to the early hyperglycaemic environment [11].…”

Section: Introductionmentioning

confidence: 99%

Novel insights into DNA methylation and its critical implications in diabetic vascular complications

et al. 2017

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Recent epidemiological and clinical studies have shown that type 2 diabetic patients can develop diabetic vascular complications even after intensive glycaemic control. It has been suggested that this phenomenon could be explained by the hypothesis of ‘metabolic memory’. The underlying mechanisms between these enduring effects and the prior hyperglycaemic state are still not well understood. Preliminary studies demonstrate that hyperglycaemia can regulate gene expression by epigenetic modifications, such as DNA methylation, which can persistently exist even after glucose normalization. Increasing evidence shows that epigenetic mechanisms may play a substantial role in the pathophysiology of diabetes and its associated vascular complications, including atherosclerosis, diabetic cardiomyopathy (DCM), nephropathy and retinopathy. In this review, we will examine the growing role of DNA methylation in diabetes and its vascular complications, thus it can provide critical implications for the early prevention of diabetes and its vascular complications.

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Importance of Metabolic Memory in the Development of Vascular Complications in Diabetic Patients

Cited by 17 publications

References 84 publications

Systems Immunology of Diabetes-Tuberculosis Comorbidity Reveals Signatures of Disease Complications

Systems Immunology of Diabetes-Tuberculosis Comorbidity Reveals Signatures of Disease Complications

Genetic and epigenetic modifications in the pathogenesis of diabetic retinopathy: a molecular link to regulate gene expression

Novel insights into DNA methylation and its critical implications in diabetic vascular complications

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