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.