This study aimed to determine ANGPTL3 serum levels in healthy young lean and obese non-diabetic men during an oral glucose tolerance test (OGTT) and correlate them with anthropometric, biochemical and hormonal parameters. A case–control study was carried out and 30 young obese non-diabetic (23.90 ± 3.84 years and BMI 37.92 ± 4.85 kg/m2) and 28 age-matched healthy lean (24.56 ± 3.50 years and BMI of 22.10 ± 1.72 kg/m2) men were included in this study. The primary outcome measures were serum basal ANGPTL3 and ANGPTL3–area under the curve (AUC) levels. The percentage of body fat was measured by dual-energy X-ray absorptiometry and biochemical, hormonal and insulin resistance indices were determined. Basal ANGPTL3 and ANGPTL3–AUC levels were significantly elevated (p < 0.05) in young obese subjects compared with lean subjects and were positively and significantly associated with different anthropometric measurements. Fasting ANGPTL3 serum levels were positively correlated with fasting insulin, leptin, Leptin/Adiponectin index and triglyceride—glucose index. Moreover, ANGPTL3–AUC was negatively correlated with Matsuda index. In this regard, chronically high ANGPTL3 levels in young obese subjects might favor triglyceride-rich lipoprotein clearance to replenish triglyceride stores by white adipose tissue rather than oxidative tissues.

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.

Context Leptin is an adipokine involved in many pleiotropic and key physiological actions and circulates free and active, or inactive bound to the leptin binding protein and sOB-r. Thus, the ratio Leptin/sOB-r or free leptin index (FLI) is commonly used as a marker of leptin sensitivity in different pathologies. Objective Evaluate serum concentrations of leptin and sOB-r and determine FLI in healthy pregnant and mild pre – eclamptic women in the three trimesters of gestation. Design A nested case-control study within a prospective cohort study of pregnant women, enrolled in the Department of Obstetrics and Gynecology of the School of Medicine at Universidad Nacional. Main Outcome Measure and Methods From the initial cohort, 46 healthy pregnant women and 19 mild pre – eclamptic pregnant women were randomly selected. Anthropometric, biochemical and clinical parameters were determined during three stages of pregnancy [1st (11.3±2.3 weeks), 2nd (24.4±3.10 weeks) and 3rd (34.84±4.41 weeks) periods of gestation]. Data were presented as mean ± SD. A p value &lt;0.05 was considered to be statistically significant. Results Serum leptin levels and sOB-r levels rose significantly throughout pregnancy in both healthy women [Leptin (1st 23.28±9.87 ng/mL; 2nd 34.58±18.45 ng/mL; 3rd 38.27±19.64 ng/mL trimester) (p=0.0001); sOB-r (1st 32.12±7.29 ng/mL; 2nd 43.26±9.25 ng/mL; 3rd 45.16±10.70 ng/mL trimester) (p&lt;0.0000)] and preeclamptic women [Leptin (1st 29.91±9.91 ng/mL; 2nd 47.10±25.70 ng/mL; 3rd 63.00±3012 ng/mL trimester) (p&lt;0.0000); sOB-r (1st 32.09±6.97 ng/mL; 2nd 37.54±6.33 ng/mL; 3rd 36.96±7.66 ng/mL trimester) (p=0.0380)]. Serum leptin levels were significantly higher in preeclamptic pregnant women compared to healthy pregnant women at 2nd (p=0.029) and 3rd trimesters of pregnancy (p&lt;0.000). Additionally, serum sOB-r levels were also significantly lower in pre - eclamptic pregnant women during the 2nd (p=0.017) and 3rd trimester (p=0.0036) of pregnancy compared to healthy pregnant women. As a result, the FLI index did not vary significantly during any of the three periods of pregnancy studied in healthy pregnant women [(1st 7.99±4.85; 2nd 8.72±6.5; 3rd 9.15±5.84 trimester) (p &gt;0.05)], whereas, in contrast, this index markedly increased throughout pregnancy in pre - eclamptic women [(1st 8.69±4.96; 2nd 13.54±8.78; 3rd 18.06±10.35 trimester) (p=0.0044)]. Indeed, the FLI index was significantly higher at 2nd (p=0.0186) and 3rd (p&lt;0.000) trimesters of pregnancy in pre - eclamptic women compared to healthy pregnant. Conclusions The present results demonstrate for the first time in a longitudinal study that FLI increases significantly in pre - eclamptic pregnant women towards the end of pregnancy. Hence, high FLI index values should be further explored as a potentially valuable indicator for the clinical manifestations of this pathology.

Gestation is a diabetogenic state due to insulin resistance. Pregnant women with higher insulin resistance are at risk of developing preeclampsia and vascular dysfunction. Fasting glucose to insulin ratio (G 0 /I 0 ) and Fasting Insulin Resistance Index (FIRI = (G 0  x I 0 )/25) are surrogate indices of insulin sensitivity of the euglycemic-hyperinsulinemic clamp. The aim of this study was to determine G 0 /I 0  and FIRI in normal (n = 142) and preeclamptic pregnancies (n = 18), during the three periods of gestation, and three months postpartum. Also, 52 healthy non-pregnant women were studied. The study was approved by the Ethics Committee of the Faculty of Medicine and the participants provided written informed consent. A serum biochemical analysis of fasting insulin, blood glucose, total cholesterol, triglyceride and HDL cholesterol was done. G 0 /I 0  and FIRI were calculated. Statistical analyzes were performed with R software. In healthy pregnancy, G 0 /I 0  decreased significantly in the second (8.5 ± 4.3) and third periods (6.7 ± 3.0), compared to the first one (11.1 ± 5.7), non-pregnant women (11.3 ± 7.0) and postpartum (13.1 ± 7.9) (p<0.01). In preeclamptic patients, G 0 /I 0  decreased significantly from the first period (7.1 ± 1.6) to the end of pregnancy (6.2 ± 4.2) (p<0.05). In these women, G 0 /I 0  rose in the postpartum period (7.6 ± 4.4) without reaching the values of non-pregnant women (11.3 ± 7.0). The difference in the G 0 /I 0 , between healthy pregnant and preeclamptic women was due to the increase in basal insulin. A significant correlation was found between G 0 /I 0  and QUICKI, HOMA-IR and FIRI indices, during the three gestation periods and postpartum in healthy and preeclamptic, and in non-pregnant women. In healthy pregnancy, FIRI decreased significantly (p <0.05) in the first period (27.4 ± 13.7), and increased in the third period (38.4 ± 16.1 compared with non-pregnant women 33.3 ± 16.0), and decreased significantly (p <0.05) in the postpartum (27.7 ± 17.3 (p<0.01)). In preeclamptic women, the FIRI increased significantly from the second period (47.3 ± 13.7) to the end of pregnancy (45.7 ± 21.5) (p <0.05) and in postpartum (48.5 ± 28.1), compared with non-pregnant women (33.3 ± 16.0). The FIRI was not different in the third period of gestation between healthy pregnant and preeclamptic women. The FIRI was correlated with QUICKI, HOMA-IR and G 0 /I 0  indices during the different periods of pregnancy and postpartum, in healthy pregnant and preeclamptic women, and with ...