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Context  Delta like noncanonical notch ligand 1 ( DLK1 ) is a paternally expressed imprinted gene that encodes an epidermal growth factor repeat-containing transmembrane protein. A bioactive, truncated DLK1 protein is present in the circulation and has roles in development and metabolism.    Objective  We sought to investigate links between maternal pregnancy circulating DLK1 concentrations and: (1) maternal and fetal  DLK1  genotypes, (2) maternal insulin resistance and secretion, and (3) offspring size at birth.    Patients, design, and setting  We measured third-trimester maternal serum DLK1 concentrations and examined their associations with parentally transmitted fetal and maternal  DLK1  genotypes, indices of maternal insulin resistance and secretion derived from 75-g oral glucose tolerance tests performed around week 28 of pregnancy, and offspring size at birth in 613 pregnancies from the Cambridge Baby Growth Study.    Results  Maternal DLK1 concentrations were associated with the paternally transmitted fetal  DLK1  rs12147008 allele ( P  = 7.8 × 10 -3 ) but not with maternal rs12147008 genotype ( P  = 0.4). Maternal DLK1 concentrations were positively associated with maternal prepregnancy body mass index ( P  = 3.5 × 10 -6 ), and (after adjustment for maternal body mass index) with both maternal fasting insulin resistance (Homeostatic Model Assessment of Insulin Resistance:  P  = 0.01) and measures of maternal insulin secretion in response to oral glucose (insulinogenic index:  P  = 1.2 × 10 -3 ; insulin disposition index:  P  = 0.049). Further positive associations were found with offspring weight ( P  = 0.02) and head circumference at birth ( P  = 0.04).    Conclusion  These results are consistent with a partial paternal or placental origin for the maternal circulating DLK1 which may lead to increased maternal circulating DLK1 concentrations, stimulation of maternal insulin resistance and compensatory hyperinsulinemia during pregnancy, and the promotion of fetal growth.

Pregnancy Serum DLK1 Concentrations Are Associated With Indices of Insulin Resistance and Secretion