Early-life Programming of Type 2 Diabetes Mellitus: Understanding the Association between Epigenetics/Genetics and Environmental Factors

Abstract

Type 2 Diabetes Mellitus is an increasing public health problem that poses a severe social and economic burden affecting both developed and developing countries. Defects in insulin signaling itself are among the earliest indications that an individual is predisposed to the development of insulin resistance and subsequently Type 2 Diabetes Mellitus. To date, however, the underlying molecular mechanisms which result in resistance to the actions of insulin are poorly understood. Furthermore, it has been shown that maternal obesity is associated with an increased risk of obesity and insulin resistance in the offspring. However, the genetic and/or epigenetic modifications within insulin-sensitive tissues such as the liver and skeletal muscle, which contribute to the insulin-resistant phenotype, still remain unknown. More importantly, a lack of in-depth understanding of how the early life environment can have long-lasting effects on health and increased risk of Type 2 Diabetes Mellitus in adulthood poses a major limitation to such efforts. The focus of the current review is thus to discuss recent experimental and human evidence of an epigenetic component associated with components of nutritional programming of Type 2 Diabetes Mellitus, including altered feeding behavior, adipose tissue, and pancreatic beta-cell dysfunction, and transgenerational risk transmission.

Improvement in glucose metabolism in adult male offspring of maternal mice fed diets supplemented with inulin via regulation of the hepatic long noncoding RNA profile

“…The traditional environmental risk factors for diabetes include dietary habits, such as overnutrition, undernutrition and unbalanced nutrition 2 . Currently, in addition to reporting on lifestyle changes in adulthood, an increasing number of epidemiological and experimental studies have focused on the effect of maternal nutrition status on metabolic disease incidence in offspring 3,4 . Environmental factors present in a young child's life are considered origins of metabolic disease incidence during adulthood.…”

“…2 Currently, in addition to reporting on lifestyle changes in adulthood, an increasing number of epidemiological and experimental studies have focused on the effect of maternal nutrition status on metabolic disease incidence in offspring. 3,4 Environmental factors present in a young child's life are considered origins of metabolic disease incidence during adulthood. These environmental factors are critical for organ and tissue development and, thus, may exert metabolic programming effects that can render individuals more prone to developing metabolic diseases later in life.…”

Hyperglycemia First Detected in Pregnancy in South Africa: Facts, Gaps, and Opportunities

“…Many studies report telomere shortening in placentas from pregnancies with uncontrolled diabetes and GDM (113)(114)(115). Telomere shortening is also linked with future diabetes and cardiovascular disease in mothers and offspring (116)(117)(118). A better understanding of telomere homeostasis in GDM may illuminate some of the mechanisms underpinning health and disease's developmental origins.…”

The Critical Role of Epigenetic Regulation in Developmental Programming of Higher Organisms

“…In this review, the authors also evaluate the relationships existing between the HOX and GATA master regulators and microRNA (miRNA) pathways. Lastly, Kadayifci et al [7] discuss the importance of the epigenetic mechanisms for the nutritional programming of Type 2 Diabetes Mellitus and their roles in the developmental origin of this worldwide chronic disease.…”