Elevated Cholesteryl Ester Transfer Protein Activity Early in Pregnancy Predicts Prediabetes 5 Years Later

Abstract

Abstract Context Cholesteryl ester transfer protein (CETP) regulates high-density lipoprotein (HDL) cholesterol levels and interaction between glucose, and HDL metabolism is central in the development of diabetes. Objective We hypothesized that CETP levels would be regulated in diabetic pregnancies. We tested the hypothesis by evaluating CETP activity measured multiple times during pregnancy and at 5 years’ follow-up in a prospective cohort (STORK) and investigated its association with gestational diabetes mellitus (GDM) during pregnancy or development of prediabetes 5 years after pregnancy. We also evaluated the strongest correlation of CETP activity among measures of adipocity and glucose metabolism, lipoproteins, adipokines, and monocyte/macrophage activation markers. Design A population-based longitudinal cohort study was conducted from 2001 to 2013. Setting The study setting was Oslo University Hospital. Patients or Other Participants A total of 300 women during pregnancy and at 5 years postpartum participated in this study. Main Outcome Measures CETP activity was measured at 14 to 16, 22 to 24, 30 to 32, and 36 to 38 weeks’ gestation, and at 5 years’ follow-up. Results We found higher CETP activity in pregnancy in women developing prediabetes but no association with GDM. CETP activity decreased throughout pregnancy and remained low at follow-up. High CETP activity was associated with sCD14 levels, in particular in women who developed prediabetes. These data show that enhanced CETP activity during pregnancy is associated with systemic indices of monocyte/macrophage activation, in particular in women who develop prediabetes later in life. Conclusions CETP activity during pregnancy identifies women at risk for later diabetes development.