Normalizing Metabolism in Diabetic Pregnancy: Is It Time to Target Lipids?

Maternal lipoprotein metabolism in late pregnancy. In the last trimester, elevated maternal insulin resistance and estrogen levels produce multiple changes in lipoprotein metabolism. These include a reduction of LPL activity in adipose tissue and serum, a reduction in hepatic lipase (HL), and an enhancement of the activity of cholesterol ester transfer protein (CETP). These alterations result in increased adipose tissue lipolysis, increasing the release of free fatty acids (FFAs) and glycerol from adipose tissue and their transfer to the liver and placenta. These substrates are used in the liver for gluconeogenesis, VLDL production, and ketone body synthesis and by the placenta. The VLDL produced in the liver has a higher triglyceride concentration than in the nonpregnant population. CETP activity transfers triglycerides from VLDL to LDL and HDL. HDL_2b increases more than the other HDL subfractions, due to a decrease in hepatic lipase activity and increased lecithin-cholesterol acyltransferase (LCAT) activity. In the fasting state, hepatic gluconeogenesis and hepatic β-oxidation are greatly increased, resulting in ketone body synthesis, providing potential alternative maternal fuel supplies and maintaining other substrate loads for fetal utilization. The mammary gland has increased LPL activity in late gestation and lactation. FFAs, cholesterol, glucose, ketone bodies, and amino acids can all be metabolized in the placenta. *Exaggerated in diabetic pregnancy. +See Fig. 2. This figure has been based in part on Herrera and Ortega-Senovilla (3). AA, amino acid; IR, insulin resistance; TG, triglyceride.