BackgroundWorldwide there is a high prevalence of 25-hydroxyvitamin D (25OHD) deficiency and has been associated with adverse outcomes during pregnancy.ObjectiveThis is a nested, case–control study in a longitudinal cohort to compare the serum 25OHD levels and other biomarkers throughout pregnancy in a group of 20 preeclamptic women and 61 healthy pregnant women. An additional group of 29 healthy non-pregnant women were also studied during the two phases of the menstrual cycle.ResultsMean 25OHD levels in non-pregnant women were 31.9 ng/mL and 34.9 ng/mL during follicular and luteal phase, respectively (P < 0.01). Mean serum 25OHD levels in healthy pregnant women were 26.5, 30.1 and 31.9 ng/mL, at first, second and third trimester, respectively (P < 0.001). The first trimester levels of 25OHD were lower than those of healthy non-pregnant women (P < 0.001), showing a significant recovery at third trimester. In the group of healthy pregnant women, the 25OHD levels were 25.7 ng/mL and 27.2 ng/mL at 3 and 6 months postpartum, respectively; both values were lower than those observed in the non-pregnant women (P < 0.001). In preeclamptic women, 25OHD serum levels were similar to those of healthy pregnant women; nevertheless, they remained almost unchanged throughout pregnancy.ConclusionThere were no significant differences between healthy and preeclamptic pregnant women in terms of 25OHD levels throughout the pregnancy. Serum 25OHD levels in non-pregnant women were higher during luteal phase compared with follicular phase. The 25OHD levels of non-pregnant women tended to be higher than those of pregnant women.

The Liver-Expressed Antimicrobial Peptide 2 (LEAP-2) has emerged as an endogenous GHS-R antagonist and blunts the orexigenic action of ghrelin. This study aimed to determine the Ghrelin/LEAP-2 ratio in humans and rats during pregnancy. In humans, we conducted a nested case-control study within an observational prospective cohort. Healthy and mild preeclamptic pregnant women were studied at each trimester of gestation and three months postpartum. In addition, a group of non-pregnant women was studied into the follicular and luteal phases of the menstrual cycle. Furthermore, Ghrelin/LEAP-2 ratio was investigated in non-pregnant rats and at different periods of rat pregnancy. Human and rat serum ghrelin and LEAP-2 levels were determined using the commercially available ELISA kits. The Ghrelin/LEAP-2 ratio peak around the second trimester of gestation in healthy pregnant women (p < 0.05). Additionally, there were no statistically significant differences in Ghrelin/LEAP-2 ratio between healthy and preeclamptic pregnant women at each trimester of gestation (p > 0.05). The Ghrelin/LEAP-2 ratio in pregnant rat reached the peak around mid-gestation with a similar pattern to the human pregnancy. LEAP-2 was visualized by immunohistochemistry in human term placenta and rat placentas on days 12, 16 and 21 of pregnancy. In conclusion, this study provides the first evidence of a Ghrelin/LEAP-2 ratio peak around the half-way point of pregnancy onwards during human and rat pregnancy, and it might be associated with increased rates of weight gain during pregnancy. Thus, this study suggests that LEAP-2 and Ghrelin/LEAP-2 ratio might play an important role in maternal physiology adaptation of weight gain during pregnancy.

Ghrelin is an orexigenic gastric peptide hormone implicated in pleiotropic functions, playing an important role in the regulation of food intake and homeostatic body weight regulation mediated through the growth hormone secretagogue receptor (GHSR). Recently, the liver and small intestine–derived peptide liver enriched antimicrobial peptide-2 (LEAP-2) was characterized to acts as an endogenous GHSR antagonist and blunts the orexigenic action of ghrelin. On the other hand, physiologic maternal weight gain during each trimester of pregnancy might be associated primarily with the developing fetus and the maternal energy requirements. This study aimed to determine serum LEAP-2 levels and Ghrelin/Leap-2 ratio in pregnant women at each trimester of gestation and three months postpartum. We conducted a nested study within an observational prospective cohort study. Twenty five healthy women were longitudinally studied during the first, second and third trimester of pregnancy and three months postpartum. Additionally, twenty healthy non – pregnant women were studied during the follicular a luteal phase of the menstrual cycle. Biochemical and hormonal laboratory measurements were performed during the early morning hours (07: 00-08: 00 hours) following an overnight fast (9: 00-10: 00 hours). Human serum Ghrelin (MBS283919) and LEAP-2 (MBS917663) levels were determined using the commercially available ELISA kits and the ratio between circulating Ghrelin and Leap-2 (Ghrelin/Leap-2) levels was calculated. The clinical and biochemical parameters in the studied population of pregnant women and non – pregnant women were described. In healthy pregnant women, circulating Ghrelin levels decreased significantly in the third trimester of gestation (p&lt;0.05). Also, serum Ghrelin levels are markedly increased after delivery and reaching the levels from first trimester of pregnancy (p&gt;0.05). Additionally, in healthy pregnant women, a significant decrease was observed in serum LEAP-2 concentrations from second to third trimesters of pregnancy (p&lt;0.05). In addition, serum LEAP-2 levels were significantly increased after delivery and returned to the levels of the first trimester of gestation. The Ghrelin/Leap-2 ratio increases significantly during pregnancy and reaches its peak in the second and third trimester of gestation in healthy pregnant women (p&lt;0.05). In conclusion, this study provides the first evidence that Ghrelin/Leap-2 ratio increase steadily during pregnancy reaching their peak in the second and third trimester of pregnancy. Additionally, the findings of this study suggest that Ghrelin/Leap-2 ratio might play an important role in maternal physiology adaptation of weight gain during pregnancy. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

The ratio between circulating levels of leptin and soluble leptin receptor (sOB‐R), the free leptin index (FLI), is used as a marker of leptin resistance. Therefore, the aim of our study was to investigate the FLI in mild pre‐eclamptic pregnancies in a nested case–control study within a prospective observational study. Circulating levels of leptin and sOB‐R levels rise significantly during pregnancy in healthy ( p < 0.05) ( n = 46) and pre‐eclamptic pregnancies ( p < 0.05) ( n = 20). Serum levels of leptin were significantly higher in pre‐eclamptic compared to healthy pregnancies at second and third trimesters of pregnancy ( p < 0.05). Additionally, serum levels of sOB‐R were significantly lower in pre‐eclamptic pregnancies during the second and third trimesters of pregnancy compared to healthy pregnancies ( p < 0.05). Moreover, we found that FLI did not vary significantly during pregnancy in healthy women ( p > 0.05), while it increases in pre‐eclamptic pregnancies ( p < 0.05). Indeed, FLI was significantly higher at second and third trimesters of pregnancy in pre‐eclamptic compared to healthy pregnancies ( p < 0.05). In addition, FLI was significantly higher in the luteal phase compared with the follicular phase of the menstrual cycle in eumenorrheic women ( p < 0.05). Receiver operating characteristic (ROC) curve analysis revealed the ability of leptin (AUC = 0.72) and FLI (AUC = 0.67) as a reliable predictor for mild pre‐eclampsia during the second trimester of pregnancy. In conclusion, our findings show that FLI were significantly increased in mild pre‐eclamptic pregnancies and allowed us to hypothesize that this rise might alter leptin bioavailability and bioactivity which might lead to the sympathetic hyperactivity and the hypertensive disorders during pregnancy.

Introducción: Los niveles no suficientes de vitamina D (VD) se han asociado a varias patologías no osteomusculares, sin embargo, es motivo de controversia si estos se asocian a mayor prevalencia de síndrome metabólico (SM). Objetivo: Determinar y comparar la frecuencia de insuficiencia y deficiencia de 25-Hidroxivitamina D (25(OH)D) entre hombres jóvenes obesos no diabéticos y controles con peso normal, y su correlación con el estado de síndrome metabólico. Materiales y métodos: Estudio de corte transversal, que incluyó 62 individuos con peso normal y 47 en obesidad, se determinaron los niveles séricos de 25(OH)D. y se midieron parámetros antropométricos y bioquímicos para establecer criterios de SM. Resultados: De los 47 sujetos con obesidad, 25 tenían SM, mientas que ninguno de los sujetos de peso normal cumplía con dichos criterios, No se encontraron diferencias estadísticamente significativas en cuanto a la presencia de síndrome en correlación con los niveles de vitamina D (p=0,94).. La media de los niveles séricos de 25(OH)D para la población total fue de 30,64 ng/mL; en sujetos normopeso 30,8 ng/mL y entre los obesos fue de 30,1 ng/mL con SM y 30,6 ng/mL. Por otro lado no hubo una correlación significativa entre los parámetros individuales de síndrome metabólico y los niveles séricos de VD tanto de manera global como en el análisis por subgrupos. Conclusión: No hubo una correlación significativa entre los niveles séricos de 25(OH)D con el estado de SM, tampoco se identificó ningún tipo de correlación significativa entre estos y los parámetros antropométricos y bioquímicos estudiados.