Anna Zonenberg

High resistin and interleukin-6 levels are associated with gestational diabetes mellitus.

Resistin is a cysteine-rich adipokine originally described as a molecular link between obesity and insulin resistance in rodents. In this study, we hypothesised that serum resistin concentrations are elevated in patients with gestational diabetes mellitus (GDM) when compared with pregnant women with normal glucose tolerance (NGT) and related to proinflammatory interleukin-6 (IL-6) and other factors conferring insulin resistance. Serum resistin and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA) in 81 women with GDM, 82 women with NGT between 24 and 31 weeks of gestation and 25 healthy non-pregnant women. Resistin concentrations were significantly higher in the GDM (21.9 [17.55–25.40] ng/ml) than in the NGT group (19.03 [15.92–23.91] ng/ml, p = 0.047), as well as in the non-pregnant women (14.8 [13.7–16.6] ng/ml, p < 0.0001). Serum IL-6 levels were elevated in the GDM (1.0 [0.7–1.5] pg/ml) as compared with the NGT group (0.8 [0.5–1.1] pg/ml, p = 0.006) and the non-pregnant controls (0.7 [0.5–1.1] pg/ml, p = 0.04). Multiple regression analysis revealed that in the pregnant women circulating resistin was related to serum IL-6 (β = 0.33, p = 0.0004) but not to insulin or the index of insulin resistance. It is concluded that the finding of high resistin and IL-6 levels in women with gestational diabetes might confirm a role of low-grade inflammation in the pathogenesis of GDM.

Plasma apelin levels and apelin/APJ mRNA expression in patients with gestational diabetes mellitus

AIMS AND METHODS Apelin is a novel adipokine identified as an endogenous ligand of the G protein-coupled receptor APJ. In this study we compared plasma apelin concentrations in 101 patients with gestational diabetes (GDM) and 101 women with normal glucose tolerance (NGT) between 24 and 32 weeks of gestation (Group 1), as well as in 20 women with GDM and 16 subjects with NGT at term (Group 2). Apelin and APJ mRNA expression in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placental tissue were also measured in Group 2, using quantitative real-time PCR. RESULTS There were no significant differences in plasma apelin levels between the women with GDM and NGT (Group 1: 1555.6 [1281.2-1804.2]pg/ml vs 1656.5 [1430.2-1852.1]pg/ml, Group 2: 1607.9 [1453.4-1768.7]pg/ml vs 1493.8 [1316.8-1956.7]pg/ml) nor in apelin and APJ mRNA expression in SAT, VAT and placental tissue. Apelin mRNA expression was approximately 10 fold higher in placental than in adipose tissue (p<0.0001). Apelin and APJ mRNA expression correlated significantly in SAT (R=0.45, p=0.03), VAT (R=0.69, p=0.003) and placental tissue (R=0.37, p=0.03). CONCLUSIONS No associations between circulating apelin or apelin/APJ mRNA expression and GDM or the indices of insulin resistance were noted in our study.

Visfatin in gestational diabetes: Serum level and mRNA expression in fat and placental tissue

AIMS AND METHODS In this study we measured: (1) serum visfatin concentrations in pregnant women with normal glucose tolerance (NGT) and gestational diabetes mellitus (GDM) between 26 and 33 weeks of gestation, using two immunoassays: EIA and ELISA; (2) serum visfatin levels (ELISA) and its mRNA expression (quantitative real-time PCR) in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placental tissue from women with NGT and GDM at term. RESULTS Visfatin concentrations (measured by EIA and ELISA) did not differ in the women with GDM and NGT between 26 and 33 weeks of gestation but were significantly lower in GDM than in NGT subjects at term (2.7 [0.7-4.6] vs 5.2 [3.7-5.9]ng/ml, p=0.02). There was no difference in visfatin mRNA expression in fat and placental tissue between the two subgroups. Regression analysis revealed that visfatin mRNA expression was significantly related to interleukin-6 and tumour necrosis factor-alpha mRNA expression in SAT (beta=0.39, p=0.009 and beta=0.47, p=0.002) and placental tissue (beta=0.37, p=0.03 and beta=0.49, p=0.005). CONCLUSIONS Circulating visfatin was significantly lower in the GDM than in the NGT subjects at term, although no differences in its mRNA expression in fat and placental tissues were observed.

Circulating pro- and anti-inflammatory cytokines in Polish women with gestational diabetes.

In this study we measured serum concentrations of proinflammatory interleukin-6, interleukin-8, and interleukin-18 as well as anti-inflammatory interleukin-10 in 30 pregnant women with normal glucose tolerance, in 32 women with abnormal results of a 50-g glucose challenge test, and in 57 patients with gestational diabetes mellitus. Patients with gestational diabetes had significantly higher IL-6 (median 1.0 [0.7-1.5] vs. 0.7 [0.4-0.8] pg/ml, p=0.001), IL-8 (2.1 [1.1-4.2] pg/ml vs. 0.7 [0.4-0.9] pg/ml, p<0.0001), and IL-18 (249.3 [188.5-318.7] pg/ml vs. 186.7 [139.9-243.9] pg/ml, p=0.005) as well as lower IL-10 levels than healthy pregnant women (0.6 [0.5-1.5] pg/ml vs. 2.9 [1.8-3.2] pg/ml, p<0.0001). After adjusting for glucose, insulin, and BMI values, the differences in IL-8 and IL-18 became insignificant, whereas the differences in IL-6 and IL-10 levels remained highly significant (p<0.0001). The subjects with abnormal glucose challenge test results had higher IL-6 levels (0.9 [0.7-1.3] pg/ml, p=0.005) and similar levels of other cytokines as compared with the women with normal glucose tolerance. Our results suggest an impaired balance between circulating pro- and anti-inflammatory cytokines in patients with gestational diabetes; however, a significant contribution of maternal obesity to the increased levels of IL-8 and IL-18 should be underlined.

Ghrelin in Gestational Diabetes: Serum Level and mRNA Expression in Fat and Placental Tissue

OBJECTIVES We studied the effect of an oral glucose load on circulating ghrelin, as well as ghrelin and ghrelin receptor (GHS-R1a) mRNA expression in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placental tissue from pregnant women with gestational diabetes (GDM) and normal glucose tolerance (NGT). METHODS Plasma total ghrelin levels were measured in 58 patients with GDM and 61 women with NGT by radioimmunoassay. Ghrelin and GHS-R1a mRNA expression was studied in 16 subjects with GDM and 20 healthy pregnant women at term, using RT-PCR. RESULTS Basal ghrelin concentrations and the maximal decrease in ghrelin levels after glucose load did not differ in the women with GDM and NGT (399.1 [299.6-563.3] pg/ml vs. 400.9 [302.3-475.8] pg/ml and 127.6 [23.1-213.1] pg/ml vs. 101.7 [44.0-217.6] pg/ml, respectively). Ghrelin mRNA expression in placental tissue was significantly higher in the subjects with GDM than in the healthy pregnant women (0.06 [0.03-0.07] AU vs. 0.02 [0.015-0.03 AU], p=0.02), whereas GHS-R1a mRNA expression in all three tissues studied did not differ between the two groups. Multiple regression analysis revealed that ghrelin mRNA expression in SAT was significantly predicted by serum insulin (beta=0.62, p=0.01), explaining 42% of its variability. CONCLUSIONS Ghrelin mRNA expression in placental tissue was higher in the GDM than in NGT subjects, whereas no association between circulating ghrelin and GDM was observed.

Retinol-binding protein 4 in adipose and placental tissue of women with gestational diabetes

In the present study, we evaluated serum levels of retinol-binding protein 4 (RBP4) and the expression of RBP4, glucose transporter-4 (GLUT4) and peroxisome proliferator activated receptor gamma (PPARγ) mRNA (using quantitative real time-PCR) in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placental tissue obtained from patients with gestational diabetes (GDM) and healthy pregnant women. Serum RBP4 concentrations and its expression in SAT were higher in the women with GDM than in the controls (p = 0.03). No association between serum or tissue RBP4 and the indices of insulin resistance was noted. In the GDM group serum RBP4 correlated with its mRNA expression in SAT (r = 0.67, p = 0.007). Stepwise regression analysis revealed that RBP4 mRNA expression in SAT was independently predicted by GLUT4 mRNA expression (β = 0.59, p = 0.003) and the presence of GDM (β = 0.46, p = 0.01), whereas RBP4 mRNA expression in VAT was related to PPARγ mRNA expression (β = 0.64, p = 0.0003) and the patients age (β = −0.38, p = 0.03). In conclusion, our results suggest that the elevated expression of RBP4 in SAT may contribute to the increase in circulating RBP4 in GDM subjects.