Heredity of type 2 diabetes confers increased susceptibility to oxidative stress and inflammation

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.

Increased Oxidative Stress in Gastric Cancer Patients and Their First‐Degree Relatives: A Prospective Study from Northeastern Brazil

“…Genetic variants of oxidant-antioxidant status have been shown to increase the risk of several malignancies including, breast cancer, gliomas, and gastric cancer [ 41 , 42 ] [ 43 ]. It has been also shown that the first-degree relatives of patients with diabetes mellitus have higher levels of oxidative stress than the controls [ 44 ] [ 45 ] [ 46 ]. In this study, we found higher serum levels of lipid peroxidation, as measured by MDA in the first-degree relatives of GC patients compared with controls, even after adjustment for age, sex, and smoking.…”

A plasma metabolite score of three eicosanoids predicts incident type 2 diabetes – a prospective study in three independent cohorts

“…Oxidative stress has also been implicated in the development of complications of diabetes such as nephropathy and neuropathy [32,33]. A recent study found that individuals with heredity of type 2 diabetes have an increased susceptibility to oxidative stress and inflammation following a high-carbohydrate meal [34].…”

Amelioration of Endothelial Dysfunction in Diabetes: Role of Takeda G Protein–Coupled Receptor 5

“…Both oxidative stress and inflammation interfere with insulin signaling ( Wen and Duffy, 2017 ), leading to insulin resistance, DM, and related complications ( Baig et al, 2020 ), and these processes are considered to be important components of the pathogenesis of DM. Persistent oxidative stress and the destruction of normal cellular redox homeostasis typically occur alongside chronic inflammation and the two are highly interrelated; therefore, we will discuss their impact on ECs in diabetes together ( Mallard et al, 2020 ).…”