Developmental Origins of Cardiovascular Disease, Type 2 Diabetes and Obesity in Humans

Abstract

Fetal growth restriction and low weight gain in infancy are associated with an increased risk of adult cardiovascular disease, type 2 diabetes and the Metabolic Syndrome. The fetal origins of adult disease hypothesis proposes that these associations reflect permanent changes in metabolism, body composition and tissue structure caused by undernutrition during critical periods of early development. An alternative hypothesis is that both small size at birth and later disease have a common genetic aetiology. These two hypotheses are not mutually exclusive. In addition to low birthweight, fetal ‘overnutrition’ caused by maternal obesity and gestational diabetes leads to an increased risk of later obesity and type 2 diabetes. There is consistent evidence that accelerated BMI gain during childhood, and adult obesity, are additional risk factors for cardiovascular disease and diabetes. These effects are exaggerated in people of low birthweight. Poor fetal and infant growth combined with recent increases in childhood adiposity may underlie the high rates of disease in developing countries undergoing nutritional transition. Sub-optimal maternal nutritional status is a major cause of low birthweight globally but its impact on fetal growth in ‘well-nourished’ western populations has been inadequately studied. In experimental animals hypertension and insulin resistance can be programmed in the offspring by restricting maternal diet in pregnancy but there are currently insufficient data to determine whether maternal nutritional status and diet programme cardiovascular disease risk in humans.