Plasma Ceramides and Triglycerides Are Elevated during Pregnancy in Association with Markers of Insulin Resistance in Hutterite Women.

Abstract

Changes in maternal insulin sensitivity and circulating lipids typically occur during the metabolic transitions of pregnancy and lactation. Although ceramides can cause insulin resistance in mammals, their potential roles during pregnancy and lactation are unknown. We hypothesized that changes in lipids like ceramide and triglycerides could occur across different reproductive states and relate to insulin resistance. Our objectives were to comprehensively characterize lipids in the plasma of pregnant, lactating, and nonpregnant and nonlactating (NPNL) women, and to evaluate the relationship between ceramides and the triglyceride index, a proxy of insulin resistance. Middle-aged Hutterite women from the South Dakota Rural Bone Health Study were classified by reproductive status as nonpregnant and nonlactating (NPNL; 19 observations), pregnant (14 observations), or lactating (31 observations). Several plasma lipids were elevated in pregnancy such as ceramides, triglycerides, and total- and high-density lipoprotein cholesterol. The triglyceride index was highest during pregnancy and was positively associated with long- and very long-chain ceramides. Lipidomics revealed lipid signatures specific to reproductive state, including triglycerides, phosphatidylcholines, sphingomyelins, and cholesteryl esters, which were also related to the triglyceride index. Our data support the possibility that ceramides contribute to the development of insulin resistance during pregnancy, and reveal distinct lipid signatures associated with pregnancy and lactation.