Please use this identifier to cite or link to this item: https://doi.org/10.1136/bmjdrc-2019-000945
Title: Heredity of type 2 diabetes confers increased susceptibility to oxidative stress and inflammation
Authors: Baig, Sonia 
Shabeer, Muhammad 
Parvaresh Rizi, Ehsan
Agarwal, Madhur 
Lee, Michelle H 
Ooi, Delicia Shu Qin 
Chia, Chelsea
Aung, Nweni
Ng, Geelyn 
Teo, Yvonne 
Chhay, Vanna 
Magkos, Faidon 
Vidal-Puig, Antonio
Seet, Raymond CS 
Toh, Sue-Anne 
Issue Date: Jan-2020
Publisher: BMJ
Citation: Baig, Sonia, Shabeer, Muhammad, Parvaresh Rizi, Ehsan, Agarwal, Madhur, Lee, Michelle H, Ooi, Delicia Shu Qin, Chia, Chelsea, Aung, Nweni, Ng, Geelyn, Teo, Yvonne, Chhay, Vanna, Magkos, Faidon, Vidal-Puig, Antonio, Seet, Raymond CS, Toh, Sue-Anne (2020-01). Heredity of type 2 diabetes confers increased susceptibility to oxidative stress and inflammation. BMJ Open Diabetes Research & Care 8 (1) : e000945-e000945. ScholarBank@NUS Repository. https://doi.org/10.1136/bmjdrc-2019-000945
Abstract: Introduction and objectiveHeredity of type 2 diabetes mellitus (T2DM) is associated with greater risk for developing T2DM. Thus, individuals who have a first-degree relative with T2DM (FDRT) provide a natural model to study factors of susceptibility towards development of T2DM, which are poorly understood. Emerging key players in T2DM pathophysiology such as adverse oxidative stress and inflammatory responses could be among possible mechanisms that predispose FDRTs to develop T2DM. Here, we aimed to examine the role of oxidative stress and inflammatory responses as mediators of this excess risk by studying dynamic postprandial responses in FDRTs.Research design and methodsIn this open-label case-control study, we recruited normoglycemic men with (n=9) or without (n=9) a family history of T2DM. We assessed plasma glucose, insulin, lipid profile, cytokines and F2-isoprostanes, expression levels of oxidative and inflammatory genes/proteins in circulating mononuclear cells (MNC), myotubes and adipocytes at baseline (fasting state), and after consumption of a carbohydrate-rich liquid meal or insulin stimulation.ResultsPostprandial glucose and insulin responses were not different between groups. Expression of oxidant transcription factor NRF2 protein (p<0.05 for myotubes) and gene (pgroup=0.002, ptime×group=0.016), along with its target genes TXNRD1 (pgroup=0.004, ptime×group=0.007), GPX3 (pgroup=0.011, ptime×group=0.019) and SOD-1 (pgroup=0.046 and ptime×group=0.191) was upregulated in FDRT-derived MNC after meal ingestion or insulin stimulation. Synergistically, expression of target genes of inflammatory transcription factor nuclear factor kappa B such as tumor necrosis factor alpha (pgroup=0.001, ptime×group=0.007) was greater in FDRT-derived MNC than in non-FDRT-derived MNC after meal ingestion or insulin stimulation.ConclusionsOur findings shed light on how heredity of T2DM confers increased susceptibility to oxidative stress and inflammation. This could provide early insights into the underlying mechanisms and future risk of FDRTs for developing T2DM and its associated complications.
Source Title: BMJ Open Diabetes Research & Care
URI: https://scholarbank.nus.edu.sg/handle/10635/164246
ISSN: 2052-4897
DOI: 10.1136/bmjdrc-2019-000945
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