DNA Methylation as a Diagnostic and Therapeutic Target in the Battle Against Type 2 Diabetes

Abstract

Type 2 diabetes (T2D) develops due to insulin resistance and impaired insulin secretion, predominantly in genetically predisposed subjects exposed to nongenetic risk factors like obesity, physical inactivity and ageing. Emerging data suggest that epigenetics also play a key role in the pathogenesis of T2D. Genome-wide studies have identified altered DNA methylation patterns in pancreatic islets, skeletal muscle and adipose tissue from subjects with T2D compared with nondiabetic controls. Environmental factors known to affect T2D, including obesity, exercise and diet, have also been found to alter the human epigenome. Additionally, ageing and the intrauterine environment are associated with differential DNA methylation. Together, these data highlight a key role for epigenetics and particularly DNA methylation in the growing incidence of T2D.

Genome-wide DNA methylation pattern in visceral adipose tissue differentiates insulin-resistant from insulin-sensitive obese subjects

“…16 The mean magnitude of the absolute differences in beta values was small, in line with that observed in previous studies of adipose tissue. 16,[29][30][31] Although previous studies have reported global hypomethylation associated with T2D, 24 in the present study no differences were observed in the global methylation levels between IR and IS morbidly obese patients. However, the differential methylation analysis between IR and IS patients revealed genes involved in pathways associated with the function of adipose tissue, such as cell adhesion, signal transduction, and regulation of transcription.…”

“…Previous studies have highlighted the importance of epigenetic regulation as a mechanism in the pathogenesis of T2D. 24 Detailed information concerning the DNA methylome in human pancreatic islets from T2D and nondiabetic patients has been provided. 14,25 Genome-wide DNA methylation studies in human skeletal muscle from individuals with or without a family history of T2D have also indicated differential methylation in genes involved in insulin signaling and muscle function.…”

Constant molecular aging rates vs. the exponential acceleration of mortality

“…Brain and other tissues also show linear increases of DNA methylation (7). Moreover, during treatment of type 2 diabetes, skeletal muscle DNA methylation responded to exercise and to blood glucose variations (8). Intriguingly, the methylation of genes implicated in diabetes also showed correlations with glycated hemoglobin (HbA1c), a short-term marker for blood glucose exposure.…”

Artificial light-at-night – a novel lifestyle risk factor for metabolic disorder and cancer morbidity

“…DNA hyper-methylation can silence genes that are profoundly involved in the secretion of insulin and glucagon [229]. Patients with type 2 diabetes express altered GDM in skeletal muscles, adipose tissue, and pancreatic islets [230]. DNA methylation of one CpG site at the promotor glocagone-like-peptide-1 (GLP1R) receptor gene decreases the transcription levels of GLP1R and correlated positively with the body mass index [231].…”