V.3. Metabolic effects in prenatal life
A. The effects of the maternal diet on fetal development
Environmental effects play important roles in the development of the MetS in fetal life. If a pregnant woman eats too little (or food with too low calorie and protein contents), primarily the fetal brain develops, and the development of other metabolic processes does not occur. As a result of the small amount of food, the placental function is inadequate, and the glucocorticoid level increases, which causes a low birth weight. The level of the fetal GLUT-4 transporter decreases in the muscles, but is not changed in the adipose tissue. The changed metabolism leads to an increased food intake in the fetus. If a pregnant woman eats too much (or regularly eats too much fatty food), T2DM may develop during the fetal life. The fetus is then born with a high birth weight, and its food intake is increased too. In fetal rats, insulin resistance was found in the liver, and increased insulin sensitivity in the muscle, these processes worsening up to 3 months of age; moreover the insulin sensitivity decreased in the muscle.
In both cases the B cell function decreases and insulin resistance may develop, and as a consequence the MetS may develop, as verified in animal experiments. When pregnant animals were fed with a 30% restricted amount of nutrition, the offspring were born with a high insulin level. When pregnant animals were fed with a 50% restricted amount of nutrition, the Glu sensitivity in the offspring was impaired up to 1 year of age. It was found that the female progeny were more sensitive, and T2DM developed in them. Interestingly, damaged B cells were found in the F2 generation.
When pregnant animals were fed a restricted protein diet (5-8% instead of the normal 20%), damaged B cells and a decreased insulin level were found in the progeny. The decreased insulin secretion persisted lifelong. Serious Glu intolerance and insulin resistance developed up to 1 year of age in rats. The F2 generation was characterized by impaired insulin secretion.
A high fat diet in fetal life may lead to the development of insulin resistance in the adults. It is important to note that the rat model is not really suitable for the investigation of a high fat diet, because rats tolerate a high fat diet much better than humans do. To correct the differences, the high fat diet is combined with a high sugar diet, and insulin resistance therefore develops in rats.
B. The effects of placental malformations
When placental malformations (mainly due to circulatory problems) cause a pancreatic dysfunction and decreased B cell activity in the fetus, then the T2DM develops in prenatal life.
C. The role of maternal stress
Chronic stress causes a high maternal glucocorticoid level. In 1-year-old children, high blood Glu and insulin levels were found because of the glucocorticoids.
D. The role of maternal diabetes mellitus
Maternal DM causes high blood Glu levels during the development of the fetus. This damages the fetal B cells, and insulin resistance develops in these children before the adult age.