Fetal overnutrition in polynesian pregnancies and in gestational diabetes may lead to dysregulation of the adipoinsular axis in offspring

OBJECTIVE - To compare umbilical cord leptin concentrations in different ethnic groups and between pregnancies with and without gestational diabetes mellitus (GDM) in Auckland, New Zealand. RESEARCH DESIGN AND METHODS - A cross-sectional study of 116 European, Polynesian, and South Asian women and their infants with and without GDM. Maternal metabolic measures were recorded at 36 weeks' gestation, umbilical cord samples were collected at birth, and neonatal anthropometric measures were recorded 24 h after delivery. RESULTS - Compared with Europeans and South Asians, samples of Polynesian umbilical cords had higher leptin concentrations (8.7 and 9.5 vs. 14.9 ng/ml, respectively; P = 0.026). Umbilical cord samples from pregnancies complicated by GDM had higher leptin concentrations than those from normal pregnancies (22.3 vs. 13.8 ng/ml, respectively; P = 0.022). Maternal leptin concentrations at 36 weeks were similar across ethnic groups and with and without GDM. Cord leptin correlated with birth weight, measures of fetal size, and cord insulin in normal pregnancies and those complicated by GDM. In multivariate analyses, cord leptin was related to birth weight (P < 0.001), gestation at delivery (P = 0.038), and ethnic group (P = 0.017) in normal pregnancies and to birth weight (P < 0.001), gestation at deliver (P < 0.001), and sex (P = 0.003) but not maternal diabetes status (P = 0.909) in pregnancies complicated by GDM. CONCLUSIONS - Offspring of Polynesian women are relatively hyperleptinemic, independent of birth size. Offspring of women with GDM are also relatively hyperleptinemic at birth, but this was associated with their increased birth weight. We speculate that this GDM-associated relative hyperleptinemia may be due to fuel-mediated teratogenesis affecting the adipoinsular axis, which in turn could also lead to leptin resistance and obesity in adult life. The reason for the ethnic difference in hyperleptinemia is unclear.