Mechanisms underlying the association between early-life nutrient restriction and development of type 2 diabetes

In the last few decades Type 2 diabetes has become a global public health crisis with prevalence of the disease increasing at an alarming rate in most nations. In particular, the majority of new diabetes cases worldwide are projected to arise from developing countries fueled by a rapid rise in urbanization and recent changes in dietary patterns. Type 2 diabetes is a complex polygenic disease, the pathophysiology of which involves an interaction between genetic predisposition and environmental triggers. Hyperglycemia and consequent micro- and macrovascular complications develop gradually as a result of failure of pancreatic beta-cells to adequately compensate for insulin resistance, typically induced by conditions that increase metabolic demand (i.e. obesity, aging, pregnancy etc). Epidemiological and animal studies suggest that early-life nutrient availability may contribute to the adult susceptibility for diabetes. This association becomes more pronounced in individuals exposed to an abundant nutritional environment during adulthood. It is of particular importance in the developing world where lack of nutrient availability during fetal and early-life often coincides with relative nutritional abundance in adulthood. Therefore, in the current chapter we will first review current advances in understanding the pathophysiology of type 2 diabetes and, secondly, explore epidemiological evidence linking early-life nutrient availability with increased susceptibility to diabetes in adult life. Finally, authors will review physiological and molecular mechanisms linking early-life nutrient insufficiency and the onset of adult diabetes with particular focus placed on mechanisms underlying pancreatic beta-cell failure.