The Fetal Origins of Type 2 Diabetes Mellitus

Like other living creatures, human beings are “plastic” in early life and are molded by the environment. Although the growth of a fetus is influenced by its genes, studies in humans and animals suggest that this growth is usually limited by the environment, particularly by the nutrients and oxygen the fetus receives (1). There are many possible evolutionary advantages in the tendency of the body to remain plastic during development rather than have its development driven only by genetic instructions acquired at conception (2). Studies in animals show that a fetus may adapt to malnutrition by altering hormone production or the sensitivity of tissues to these hormones (3, 4). Among the hormones that regulate fetal growth, and hence the requirements for nutrients, insulin has a central role (5). The fetus can alter its metabolism (for example, by switching from glucose to amino acid oxidation) (4). It can redistribute its cardiac output to protect key organs, especially the brain. Slowing of growth is also an adaptive function because it reduces the requirements for substrate. Unlike physiologic adaptations in adulthood, adaptations during development tend to lead to permanent changes in the structure and function of the body. Experiments show that even minor modifications to the diet of pregnant animals may be followed by lifelong changes in the offspring in ways that can be related to human disease (for example, elevated blood pressure and altered glucose-insulin metabolism) (6). At a molecular level, such “programmed” changes may reflect the alteration of gene expression in utero by nutrient availability, acting directly on the …