C-Peptide and leptin system in dichorionic, small and appropriate for gestational age twins—possible link to metabolic programming?

Abstract

Children born small for gestational age (SGA) are at increased risk of future glucose intolerance and type 2 diabetes, possibly after due intrauterine metabolic programming. Soluble leptin receptor (SLR) limits leptin access to signaltransducing membrane receptors. The present study examines whether SGA and appropriate for gestational age (AGA) twins differ with regard to their C-peptide, glucose and leptin systems. The markers C-peptide, glucose, fetal leptin, and SLR in cord blood were assessed in children from dichorionic twin pregnancies at delivery. In 32 cases, weight differed by >15% between twins: one demonstrated Intrauterine Growth Retardation (IUGR) (<10th percentile-SGA), while the other did not (AGA I). The other 67 pairs presented appropriate weight for gestational age (AGA II). Placental leptin and placental leptin receptor content were also assessed. Despite the same concentrations of glucose, the SGA twins maintained a higher level of C-peptide [44.48 pmol/l vs. 20.91 pmol/l, p < 0.05] than the AGA I co-twins, higher HOMA index, calculated as [C-peptide] x [Glucose] (p = 0.045), in cord blood, and a higher level of SLR [SGA vs AGA I-mean: 28.63 ng/ml vs. 19.91 ng/ml, p < 0.01], without any differences in total leptin (p = 0.37). However, SGA placentas demonstrated higher leptin level [130.1 pg/100 g total protein vs 83.8 pg/100 g total protein, p = 0.03], without differences in placental leptin receptor (p = 0.66). SGA/IUGR twins demonstrate relative insulin resistance accompanied by decreased fetal and increased placental leptin signaling. We speculate that relative insulin resistance and changes in the leptin system might be the first evidence of processes promoting deleterious metabolic programming for post-natal life.

Cord blood adiponectin and leptin concentrations in monochorionic twins with selective intrauterine growth restriction and their associations with childhood growth trajectories

“…However, we did not find a difference in cord blood leptin concentration between sIUGR cotwins, which is in conflict with previous studies that reported lower cord blood leptin in SGA neonates in singleton neonates 30–32 but in accordance with the results presented by a similar discordant twin study 26,33 . Interestingly, we found that the cord blood leptin concentration was lower in sIUGR twin pairs than in NC twin pairs, signifying a reduction in leptin levels also found in appropriately grown neonates from sIUGR pregnancies.…”

Pathomechanisms of Prenatally Programmed Adult Diseases

“…In a recent study of weight discordant twins, it has been shown that growth-retarded twins demonstrate insulin resistance with decreased fetal and increased placental leptin levels as compared with co-twins exhibiting appropriate fetal growth. Concomitantly, soluble leptin receptor levels increased in growth-restricted twins limiting leptin access to the membranebound receptor, and thus further enhancing leptin resistance [223]. Fetal leptin derives from the placenta with a less significant contribution in the fetal adipose tissue.…”

Maternal and Placental DNA Methylation Changes Associated with the Pathogenesis of Gestational Diabetes Mellitus

“…However, leptin is a large protein molecule that cannot pass through the placental barrier, so it is independent of the maternal blood LEP and forms a separate regulatory mechanism. The placental leptin levels in the one twin with small for gestational age (SGA) were significantly higher in comparison with the other normal weight twin of a dichorionic twin pregnancy [ 37 ]. This also suggests that leptin regulation in placenta is independent in the same maternal blood environment.…”