Prenatal Malnutrition-Induced Epigenetic Dysregulation as a Risk Factor for Type 2 Diabetes

Abstract

Type 2 diabetes (T2D) is commonly regarded as a disease originating from lifestyle-related factors and typically occurring after the age of 40. There is, however, consistent experimental and epidemiological data evidencing that the risk for developing T2D may largely depend on conditions early in life. In particular, intrauterine growth restriction (IUGR) induced by poor or unbalanced nutrient intake can impair fetal growth and also cause fetal adipose tissue and pancreatic β-cell dysfunction. On account of these processes, persisting adaptive changes can occur in the glucose-insulin metabolism. These changes can include reduced ability for insulin secretion and insulin resistance, and they may result in an improved capacity to store fat, thereby predisposing to the development of T2D and obesity in adulthood. Accumulating research findings indicate that epigenetic regulation of gene expression plays a critical role in linking prenatal malnutrition to the risk of later-life metabolic disorders including T2D. In animal models of IUGR, changes in both DNA methylation and expression levels of key metabolic genes were repeatedly found which persisted until adulthood. The causal link between epigenetic disturbances during development and the risk for T2D was also confirmed in several human studies. In this review, the conceptual models and empirical data are summarized and discussed regarding the contribution of epigenetic mechanisms in developmental nutritional programming of T2D.