Epigenetics and type II diabetes mellitus: underlying mechanisms of prenatal predisposition

Abstract

Type II diabetes mellitus (T2DM) is a widespread metabolic disorder characterized by insulin resistance precipitating abnormally high blood glucose levels. While the onset of T2DM is known to be the consequence of a multifactorial interplay with a strong genetic component, emerging research has demonstrated the additional role of a variety of epigenetic mechanisms in the development of this disorder. Heritable epigenetic modifications, such as DNA methylation and histone modifications, play a vital role in many important cellular processes, including pancreatic cellular differentiation and maintenance of normal β-cell function. Recent studies have found possible epigenetic mechanisms to explain observed risk factors, such as altered atherogenic lipid profiles, elevated body mass index (BMI), and impaired glucose tolerance (IGT), for later development of T2DM in children born to mothers experiencing both famine and hyperglycemic conditions. It is suggested that these epigenetic influences happen early during gestation and are less susceptible to the effects of postnatal environmental modification as was previously thought, highlighting the importance of early preventative measures in minimizing the global burden of T2DM.

Early-Life Nutritional Programming of Type 2 Diabetes: Experimental and Quasi-Experimental Evidence

“…Interestingly, the seasonal pattern of birth was found to be very similar in type 1 and type 2 diabetic patients, suggesting shared early-life etiological causation for both disorders [97]. In more recent research by Jensen et al [98], no evidence for seasonality of birth in Danish patients with T2D was found. The authors assumed that difference in effects obtained in Denmark and the Ukraine may be explained by standards of living or by differences in latitude between the countries.…”

Genome-wide DNA methylation profiling of human diabetic peripheral neuropathy in subjects with type 2 diabetes mellitus

“…The pathogenesis of T2D and DPN is largely driven by lifestyle factors such as limited physical activity and poor diet [10]. However, there is a clear polygenic risk to developing T2D and DPN [11,12], and growing evidence suggests that in response to behavioural and environmental stressors, epigenetic mechanisms also contribute significantly to diabetes and its complications [13][14][15]. Indeed, epigenetic modifications are hypothesized as a way to bridge the gap between lifestyle factors and genetics [16].…”

Arsenic and human health effects: A review

“…Epigenetic changes have been linked with wide range of diseases involving cardiovascular(Lund and Zaina, 2011; Ordovas and Smith, 2010), cancer(Sarkar et al, 2013), neurological complications (Kleefstra et al, 2014Rudenko and Tsai, 2014) and metabolic disorders(Sterns et al, 2014). In mammals, epigenetic mechanisms are essential to maintain genomic stability, parent specific imprinting patterns, blocking endogenous retrotransposson activity(Smith et al, 2012c).…”