Surrogate indices of insulin resistance using the Matsuda index as reference in adult men-a computational approach.

Background: Overweight and obesity, high blood pressure, hyperglycemia, hyperlipidemia, and insulin resistance (IR) are strongly associated with non-communicable diseases (NCDs), including type 2 diabetes, cardiovascular disease, stroke, and cancer. Different surrogate indices of IR are derived and validated with the euglycemic-hyperinsulinemic clamp (EHC) test. Thus, using a computational approach to predict IR with Matsuda index as reference, this study aimed to determine the optimal cutoff value and diagnosis accuracy for surrogate indices in non-diabetic young adult men. Methods: A cross-sectional descriptive study was carried out with 93 young men (ages 18-31). Serum levels of glucose and insulin were analyzed in the fasting state and during an oral glucose tolerance test (OGTT). Additionally, clinical, biochemical, hormonal, and anthropometric characteristics and body composition (DEXA) were determined. The computational approach to evaluate the IR diagnostic accuracy and cutoff value using difference parameters was examined, as well as other statistical tools to make the output robust. Results: The highest sensitivity and specificity at the optimal cutoff value, respectively, were established for the Homeostasis model assessment of insulin resistance index (HOMA-IR) (0.91; 0.98; 3.40), the Quantitative insulin sensitivity check index (QUICKI) (0.98; 0.96; 0.33), the triglyceride-glucose (TyG)-waist circumference index (TyG-WC) (1.00; 1.00; 427.77), the TyG-body mass index (TyG-BMI) (1.00; 1.00; 132.44), TyG-waist-to-height ratio (TyG-WHtR) (0.98; 1.00; 2.48), waist-to-height ratio (WHtR) (1.00; 1.00; 0.53), waist circumference (WC) (1.00; 1.00; 92.63), body mass index (BMI) (1.00; 1.00; 28.69), total body fat percentage (TFM) (%) (1.00; 1.00; 31.07), android fat (AF) (%) (1.00; 0.98; 40.33), lipid accumulation product (LAP) (0.84; 1.00; 45.49), leptin (0.91; 1.00; 16.08), leptin/adiponectin ratio (LAR) (0.84; 1.00; 1.17), and fasting insulin (0.91; 0.98; 16.01). Conclusions: The computational approach was used to determine the diagnosis accuracy and the optimal cutoff value for IR to be used in preventive healthcare.

A longitudinal study of free leptin index in pre-eclamptic pregnancies.

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.

Study of the Ghrelin/LEAP-2 Ratio in Humans and Rats during Different Phases of Pregnancy.

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.

Maternal Fibroblast Growth Factor 21 Levels Decrease during Early Pregnancy in Normotensive Pregnant Women but Are Higher in Preeclamptic Women-A Longitudinal Study.

(1) Background: Fibroblast growth factor 21 (FGF-21) is an endocrine factor involved in glucose and lipid metabolism that exerts pleiotropic effects. The aim of this study was to investigate the serum FGF-21 profile in healthy and mild preeclamptic pregnant women at each trimester of pregnancy; (2) Methods: Serum FGF-21 levels were determined by ELISA in a nested case-control study within a longitudinal cohort study that included healthy (n = 54) and mild preeclamptic (n = 20) pregnant women, women at three months after delivery (n = 20) and eumenorrheic women during the menstrual cycle (n = 20); (3) Results: FGF-21 levels were significantly lower in the mid-luteal phase compared to the early follicular phase of the menstrual cycle in eumenorrheic women (p < 0.01). Maternal levels of FGF-21 were significantly lower in the first and second trimesters and peaked during the third trimester in healthy pregnant women (p < 0.01). Serum levels of FGF-21 in healthy pregnant were significantly lower in the first and second trimester of pregnancy compared with the follicular phase of the menstrual cycle and postpartum (p < 0.01). Serum FGF-21 levels were significantly higher in preeclamptic compared to healthy pregnant women during pregnancy (p < 0.01); (4) Conclusions: These results suggest that a peak of FGF-21 towards the end of pregnancy in healthy pregnancy and higher levels in preeclamptic women might play a critical role that contributes to protecting against the negatives effects of high concentrations of non-esterified fatty acids (NEFA) and hypertensive disorder. Furthermore, FGF-21 might play an important role in reproductive function in healthy eumenorrheic women during the menstrual cycle.