Metabolism in Normal & Diabetic Pregnancy

Deterioration of glucose tolerance occurs normally during pregnancy. Significant metabolic changes are necessary to provide proper energy delivery to the growing conceptus. Hormones associated with pregnancy such as human placental lactogen (HPL) and cortisol lower glucose levels, promote fat deposition, and stimulate appetite. Rising serum levels of estrogen and progesterone increase insulin production and secretion while increasing tissue sensitivity to insulin. The overall result is a lowering of the fasting glucose levels, reaching a nadir by the 12th week. The decrease is on average 15 mg/dL; thus fasting values of 70-80 mg/dL are normal in a pregnant woman by the 10th week of gestation. There is a comparable decrease in postprandial values. This acts to protect the developing embryo from elevated glucose levels. Indeed, birth defects are noted at a 2- to 3-fold higher rate in women with diabetes without preconception glycemic control. In summary, hormones associated with pregnancy facilitate maternal storage of energy in the first trimester and then assist in the diversion of energy to the fetus in later pregnancy as demand increases.

In the second trimester, higher fasting and postprandial glucose levels are seen. This facilitates the placental transfer of glucose. Glucose transfer is via a carrier-mediated active transport system that becomes saturated at 250 mg/dL. Fetal glucose levels are 80% of maternal values. In contrast, maternal amino acid levels are lowered during the second trimester by active placental transfer to the fetus. Fetal levels of amino acids are 2- to 3-fold higher than maternal levels, but not as high as levels within the placenta. Lipid metabolism in the second trimester shows continued storage until midgestation; then, as fetal demands increase, there is enhanced mobilization (lipolysis).

HPL is the hormone mainly responsible for insulin resistance and lipolysis. HPL also decreases the hunger sensation and diverts maternal carbohydrate metabolism to fat metabolism in the third trimester. HPL is a single-chain polypeptide secreted by the syncytiotrophoblast and has a molecular weight of 22,308 and a half-life of 17 minutes. HPL levels are elevated during hypoglycemia to mobilize free fatty acids for energy for maternal metabolism. HPL levels are low with maternal hyperglycemia. HPL is similar in structure to growth hormone and acts by reducing the insulin affinity to insulin receptors. The effect on the fetus is to allow longer glucose elevations for placental transfer to the developing fetus and minimizing maternal use of glucose for metabolic needs.

During pregnancy, the levels of HPL rise steadily during the first and second trimesters with a plateau in the late third trimester. This plateau is the natural result of decreasing nutrient delivery to the placenta, thus decreasing hormone production. It appears that this is a necessary signal to the developing fetus to initiate fetal cortisol and thyroid hormone release to in turn initiate enzyme development for maturation. In pregnancies with elevated glucose and other nutrients, there is continued placental growth with a delay in fetal organ/hormonal maturation. In short, mother and fetus communicate through nutrient delivery and utilization.