scholarly journals Type 2 Diabetes Mellitus: The Role of Epigenetic Modifications in Pathophysiology and Prospects for the Use of Epigenetic Therapy

2021 ◽  
Vol 7 (5) ◽  
Author(s):  
Tajudeen Yahaya

The need to reverse the growing incidence and burden of diabetes mellitus (DM) worldwide has led to more studies on the possible causes of the disease. Genetic and environmental factors had long been suspected in the pathogenesis of a form of the disease known as the Type 2 diabetes mellitus (T2DM). However, more recent studies suggest epigenetic changes could also be involved in the onset of the disease. This review highlights the role of epigenetic modifications in the pathogenesis and management of T2DM. Peer reviewed studies on the subject were retrieved from reputable sources over the internet, and the majority of the studies unanimously implicated epigenetic modifications in the pathogenesis of some cases of the disease. DNA methylation, histone modification and microRNAs mediated pathways were observed to be the main mechanisms of epigenetic changes. These mechanisms are triggered by certain environmental factors such as diets, microbial and pollutant exposure, lifestyles, among others, prior to the onset of T2DM. Epigenetic changes can modify the expressions and functions of certain genes involved in insulin biosynthesis and glucose metabolism, leading to hyperglycemia and insulin resistance, which are hallmarks of T2DM. Fortunately, epigenetic changes can be reversed by blocking or activating the modulating enzymes, thus if the epigenetic aetiology of a diabetic condition is identified, it can be used as a therapeutic strategy.


Author(s):  
Nermien Abd El Rahman Ibraheim ◽  
Fatema El Zahraa Sayed Bukhary ◽  
Yehia Zakareia Mahmoud ◽  
Mahmoud Ragab Mohamed ◽  
Salama Rabei Abdel-Rahim

2018 ◽  
Vol 15 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Sayantan Nath ◽  
Sambuddha Das ◽  
Aditi Bhowmik ◽  
Sankar Kumar Ghosh ◽  
Yashmin Choudhury

Background:Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM and its complications were often inconclusive, thus spurring the present study.Methods:Meta-analysis of 25 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in determining the risk for T2DM and 17 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in development of T2DM related complications were conducted.Results:Our study revealed an association between GSTM1 and GSTT1 null polymorphism with T2DM (GSTM1; OR=1.37;95% CI =1.10-1.70 and GSTT1; OR=1.29;95% CI =1.04-1.61) with an amplified risk of 2.02 fold for combined GSTM1-GSTT1 null genotypes. Furthermore, the GSTT1 null (OR=1.56;95%CI=1.38-1.77) and combined GSTM1-GSTT1 null genotypes (OR=1.91;95%CI=1.25- 2.94) increased the risk for development of T2DM related complications, but not the GSTM1 null genotype. Stratified analyses based on ethnicity revealed GSTM1 and GSTT1 null genotypes increase the risk for T2DM in both Caucasians and Asians, with Asians showing much higher risk of T2DM complications than Caucasians for the same. </P><P> Discussion: GSTM1, GSTT1 and combined GSTM1-GSTT1 null polymorphism may be associated with increased risk for T2DM; while GSTT1 and combined GSTM1-GSTT1 null polymorphism may increase the risk of subsequent development of T2DM complications with Asian population carrying an amplified risk for the polymorphism.Conclusion:Thus GSTM1 and GSTT1 null genotypes increases the risk for Type 2 diabetes mellitus alone, in combination or with regards to ethnicity.


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