Diabetes, Developmental Programming and Oxidative Stress

Incidence of Type 2 diabetes mellitus (T2DM) is increasing worldwide. Diabetes during pregnancy, as adverse intrauterine environment, has been shown to induce long term effects and play a crucial role in developmental programming in offspring. In utero exposure to increased maternal blood glucose concentrations is associated with cardio-vascular alterations, including hypertension and increased risk for obesity and T2DM at adulthood. Early programming of later dysfunction and disease in offspring may result from a combination of mechanisms acting at organ, tissue, cellular and molecular levels. Impaired glucose-insulin metabolism programmed during the critical window of perinatal development may contribute to epigenetic changes in gene expression. This disadvantageous intrauterine environment has been recently emphasised by the role of genetic pathways and in particular, perinatal disturbance of the oxidative state. This chapter examines the epidemiologic and mechanistic issues involved in the developmental programming of long term consequences in offspring of diabetic mothers, with a particular focus on oxidative stress. It also emphasises the mechanisms of hypertension, obesity and insulin resistance. In that considerable concern and because maternal diabetes may be a contributor to the current worldwide epidemic of T2DM, interventions aimed at optimizing maternal blood glucose concentrations during pregnancy should significantly impact T2DM epidemiology.

Keywords: Type 2 diabetes mellitus, maternal blood glucose, early programming, impaired glucose-insulin metabolism, critical window of perinatal development, oxidative state, epigenetic changes, intrauterine environment