ABSTRACT
A large body of epidemiological evidence has consistently shown that impaired intrauterine growth is associated with adult metabolic and cardiovascular disorders (CVDs), including coronary heart disease, type 2 diabetes (T2D), and insulin resistance (IR) (Curhan et al. 1996; Forsen et al. 1999; Harder et al. 2007; Osmond et al. 1993). These disorders cluster in the metabolic syndrome (MS), also known as cardiometabolic syndrome or “Syndrome X,” of which the presence of IR in various tissues was initially regarded as the underlying factor. Indeed, IR has been regarded as the main link between all disorders grouped in the MS (Reaven 1998), 310including T2D, dyslipidemia, central obesity, arterial hypertension, prothrombotic and proinflammatory states, polycystic ovary, and nonalcoholic fatty liver disease (NAFLD). From the perspective of the clinical importance, the MS has two important features that include its global prevalence that is increasing dramatically and its strong association with CVD. It is widely accepted that IR results from a complex interaction between the gene variants and the environment (Sookoian and Pirola 2007, 2011). For example, environmental factors such as decreased physical activity, increasing nutrient availability, and overfeeding play an important role in the development of metabolic disorders associated with IR, and they are widely recognized as responsible for the modern epidemic of MS and its related phenotypes. However, no environmental factors or genes by themselves explain the pathophysiology of IR and MS. This is partly explained by environmental factors operating at different levels and their influence is even more significant in a genetically predisposed ground, but so far the gene variants associated with the various components of MS together account for a very small portion variability of each phenotype (Sookoian and Pirola 2007, 2011). Therefore, it is reasonable to speculate that the interaction between genes and environment is a strong modifier of the IR state and this interaction is modulated by epigenetic mechanisms.
