The metabolic-epigenetic nexus in type 2 diabetes mellitus

Davison, Gareth W.; Irwin, Rachelle E; Walsh, Colum P.

doi:10.1016/j.freeradbiomed.2020.12.025

Cited by 19 publications

(10 citation statements)

References 153 publications

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“…However, the various components of diabetic dyslipidemia are not isolated abnormalities but are closely related to a broader spectrum of metabolism [17]. Recent research has also shown that metabolism and epigenetics are associated with a complex relationship between metabolism and DNA methylation and histone modification, and that their dysregulation leads to the onset of T2DM [42].…”

Section: Introductionmentioning

confidence: 99%

Age-Related Changes in Lipid and Glucose Levels Associated with Drug Use and Mortality: An Observational Study

Markovič

Grubelnik

Vošner

et al. 2022

JPM

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Background: The pathogenesis of type 2 diabetes mellitus is complex and still unclear in some details. The main feature of diabetes mellitus is high serum glucose, and the question arises of whether there are other statistically observable dysregulations in laboratory measurements before the state of hyperglycemia becomes severe. In the present study, we aim to examine glucose and lipid profiles in the context of age, sex, medication use, and mortality. Methods: We conducted an observational study by analyzing laboratory data from 506,083 anonymized laboratory tests from 63,606 different patients performed by a regional laboratory in Slovenia between 2008 and 2019. Laboratory data-based results were evaluated in the context of medication use and mortality. The medication use database contains anonymized records of 1,632,441 patients from 2013 to 2018, and mortality data were obtained for the entire Slovenian population. Results: We show that the highest percentage of the population with elevated glucose levels occurs approximately 20 years later than the highest percentage with lipid dysregulation. Remarkably, two distinct inflection points were observed in these laboratory results. The first inflection point occurs at ages 55 to 59 years, corresponding to the greatest increase in medication use, and the second coincides with the sharp increase in mortality at ages 75 to 79 years. Conclusions: Our results suggest that medications and mortality are important factors affecting population statistics and must be considered when studying metabolic disorders such as dyslipidemia and hyperglycemia using laboratory data.

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Section: Introductionmentioning

confidence: 99%

Age-Related Changes in Lipid and Glucose Levels Associated with Drug Use and Mortality: An Observational Study

Markovič

Grubelnik

Vošner

et al. 2022

JPM

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show abstract

“…During glucose homeostasis, 8-oxo-2́deosyguanosine (8-oxodG) residues are removed by 8-oxoguanine DNA glycosylase (OGG1) mostly via the short-patch pathway base excision repair (BER) ( Banda et al, 2017 , Scaccia et al, 2020 ). However, under glycotoxic conditions, hydroxyl radical (OH) overproduction affects DNA methylation by oxidation of guanosine to 8-oxodG, resulting in the accumulation of 8-oxodG which suppress the methylation of adjacent cytosines ( Banda et al, 2017 , Davison et al, 2021 , Scaccia et al, 2020 ). This event triggers a cascade of hypomethylation and transcriptional activation responsible for the recruitment of OGG1/TET1 complex proteins to 8-oxodG, facilitating the conversion of 5mC through to 5caC to sites of ROS-induced damage ( Davison et al, 2021 , Zhou et al, 2016 ).…”

Section: The Interplay Between Oxidative Stress Ncds and Epigenetic M...mentioning

confidence: 99%

Dietary polyphenols and their relationship to the modulation of non-communicable chronic diseases and epigenetic mechanisms: A mini-review

Borsoi

Neri-Numa

Oliveira

et al. 2023

Food Chemistry: Molecular Sciences

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“…Besides, in hyperglycemia condition in type 2 diabetes, DNA damage and gene transcription changes are observed against the background of increased ROS levels and metabolic depletion of antioxidant reserves. The complex relationship between metabolism and epigenetic changes can provide a conceptual basis for understanding how pathological stimuli operate the deve-lopment of complications in type 2 DM [ 210 ]. Studies of the ROS role in the type 2 DM etiology is promising to a large extent for the development of pharma-ceutical agents based on NOX inhibitors [ 211 ].…”

Section: The Role Of Reactive Oxygen Species In Vascular Dysfunction ...mentioning

confidence: 99%

Skin Microhemodynamics and Mechanisms of Its Regulation in Type 2 Diabetes Mellitus

et al. 2022

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The review presents modern ideas about peripheral microhemodynamics, approaches to the ana-lysis of skin blood flow oscillations and their diagnostic significance. Disorders of skin microhemodynamics in type 2 diabetes mellitus (DM) and the possibility of their interpretation from the standpoint of external and internal interactions between systems of skin blood flow regulation, based on a comparison of couplings in normal and pathological conditions, including models of pathologies on animals, are considered. The factors and mechanisms of vasomotor regulation, among them receptors and signaling events in endothelial and smooth muscle cells considered as models of microvessels are discussed. Attention was drawn to the disturbance of Ca 2+ -dependent regulation of coupling between vascular cells and NO-dependent regulation of vasodilation in diabetes mellitus. The main mechanisms of insulin resistance in type 2 DM are considered to be a defect in the number of insulin receptors and impaired signal transduction from the receptor to phosphatidylinositol-3-kinase and downstream targets. Reactive oxygen species plays an important role in vascular dysfunction in hyperglycemia. It is assumed that the considered molecular and cellular mechanisms of microhemodynamics regulation are involved in the formation of skin blood flow oscillations. Parameters of skin blood microcirculation can be used as diagnostic and prognostic markers for assessing the state of the body.

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The metabolic-epigenetic nexus in type 2 diabetes mellitus

Cited by 19 publications

References 153 publications

Age-Related Changes in Lipid and Glucose Levels Associated with Drug Use and Mortality: An Observational Study

Age-Related Changes in Lipid and Glucose Levels Associated with Drug Use and Mortality: An Observational Study

Dietary polyphenols and their relationship to the modulation of non-communicable chronic diseases and epigenetic mechanisms: A mini-review

Skin Microhemodynamics and Mechanisms of Its Regulation in Type 2 Diabetes Mellitus

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