The pathophysiological influence of leptin and the tumor necrosis factor system on maternal insulin resistance: negative correlation with anthropometric parameters of neonates in gestational diabetes

Abstract

The contribution of the tumor necrosis factor (TNF) system and leptin was studied in insulin resistance and neonatal development during the course of normal pregnancy and gestational diabetes mellitus (GDM). Thirty patients with GDM and their neonates (n = 30), 35 healthy pregnant women (15 in the first, nine in the second and 11 in the third trimester) and their neonates (n = 20), and 25 healthy matched non-pregnant women participated in the study. Significantly elevated levels of maternal TNF-alpha, sTNF receptor (R)-1 and R-2, leptin (detected by enzyme-linked immunosorbent assay) and fasting C-peptide (measured by radioimmunossay and raised body mass index (BMI) were found in GDM patients and in the third trimester of normal pregnancies. TNF-alpha, sTNFR-2, C-peptide, leptin concentrations and BMI positively correlated with each other in GDM. An inverse relationship between the body length, head circumference and body weight of the newborns, and maternal TNF-alpha, leptin and C-peptide concentrations was shown in GDM. In healthy pregnancies the maternal serum leptin level was in a negative linear correlation with the head circumference of the newborns. In conclusion, increased TNF-alpha and leptin levels may contribute to insulin resistance in GDM and in the third trimester of normal pregnancy and may negatively influence the anthropometric parameters of the newborns.

Release and regulation of leptin, resistin and adiponectin from human placenta, fetal membranes, and maternal adipose tissue and skeletal muscle from normal and gestational diabetes mellitus-complicated pregnancies

“…Correlations have been found among plasma leptin level, BMI and adipose tissue mass (particularly subcutaneous fat) in both animals and non-pregnant adults (Hamilton et al 1995, Lonnqvist et al 1995, Cseh et al 2002. Similarly, in this study, the release of leptin from adipose tissue strongly correlated with maternal body weight and BMI.…”

Do adiponectin, TNFα, leptin and CRP relate to insulin resistance in pregnancy? Studies in women with and without gestational diabetes, during and after pregnancy

“…Given that there are possible important roles for the adipocytokines in the early defects of type 2 diabetes, GDM women represent an ideal population to study these inter-relationships further. To date, there is limited cross-sectional information that TNFα may be elevated in GDM pregnancy [4,10]. Other cross-sectional reports have shown that adiponectin levels are reduced in women with GDM [6,7,11,12].…”

“…A maximum dose of 20 g was used during pregnancy and 25 g postpartum (in order to not overestimate the glucose dose based on a late pregnancy weight) and the cannula flushed with 20 mL of normal saline immediately after the IV dextrose. Samples were drawn from the same cannula at 2, 3,4,6,8,10,15,20,30,40,60,75,90 and 120 min, with flushing of the cannula with 3 mL of normal saline between each draw [17]. Samples were placed into pre-chilled tubes (serum/EDTA for TNFα, Ad, high sensitivity CRP (hsCRP), leptin and lipids; 4% sodium fluoride 25 µL/mL blood for glucose and insulin), centrifuged within 40 min and stored at −80 • C until time of assay.…”

Expression of adipokines and estrogen receptors in adipose tissue and placenta of patients with gestational diabetes mellitus

“…GDM is considered a prediabetic state, therefore it may display many abnormalities that possibly appear in the very early stages of type 2 diabetes mellitus (T2DM) (Pendegrass et al, 1995). In addition to mechanisms similar to patients with T2DM (Friedman et al, 1999 andCatalano et al, 2002), the etiopathogenesis of GDM includes the combination of the disturbed endocrine function of adipose tissue and placenta (Coughlan et al, 2001;Cseh et al, 2002;Kirwan et al, 2002;Radaelli et al, 2003;Ranheim et al, 2004 andMeller et al, 2006), and the systemic hormonal changes affecting insulin sensitivity in peripheral tissues .…”