Placental Proinflammatory State and Maternal Endothelial Dysfunction in Preeclampsia.

OBJECTIVE: To evaluate the placental and decidual gene expression and maternal and umbilical serum concentrations of tumor necrosis factor alpha, interleukin 6 (IL-6), IL-8, IL-10, IL-1 receptor antagonist (IL-1RA), intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 (VCAM-1), along with the proinflammatory/anti-inflammatory cytokine ratios in women with preeclampsia (PE) vs. women with normal pregnancy (NP), and to analyze PE classified as early- (EO) and late-onset (LO). METHODS: This cross-sectional study was performed with 50 women with PE (EO n = 30, LO n = 20) and 50 women with NP. Tissue gene expression levels were measured by real-time RT-PCR. Cytokines and adhesion molecules serum concentrations were measured by immunoassays. RESULTS: In PE, placental expression of IL-10 and IL-1RA was lower, while placental IL-8/IL-1RA ratio and maternal concentrations of VCAM-1 were higher vs. NP. In EO, placental expression of IL-10 was lower, while placental IL-8/IL-10 and IL-8/IL-1RA ratios were higher than LO and NP. Maternal concentrations of IL-6 were higher in LO than EO and NP. Throughout PE, maternal VCAM-1 concentrations were higher vs. NP. No significant differences were observed in the decidual expression and umbilical concentrations of the markers between the groups. CONCLUSION: PE associates with a proinflammatory placental state; however, EO associates with a proinflammatory placental state, while LO associates with systemic maternal inflammation. Both subtypes associated with maternal endothelial dysfunction.

Women with gestational diabetes develop glucose intolerance with high frequency within one year postpartum.

OBJECTIVE: To investigate the incidence of glucose intolerance postpartum in women with gestational diabetes (GDM) and assess body weight, cholesterol and triglyceride concentrations after delivery. METHODS: This was a study of an initial cohort of 100 women with GDM who were tested at 6 weeks, 6 months, and 1 year postpartum. Postpartum evaluations were glucose tolerance, weight and cholesterol and triglycerides. RESULTS: Impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) was present in 36.5% of 52 participants who were assessed at 6 weeks postpartum and diabetes in 17.3%; the remaining 48 women failed to return for the 3 evaluations. By 6 months, IFG/IGT was demonstrated in 55.8% and diabetes in 32.7% of the women. At 1 year, 46.2% exhibited IFG/IGT and 48% diabetes. Moreover, the weight was higher in those women who presented IFG/IGT (75.5 ± 15.2 kg, mean ± SD) and diabetes (79.0 ± 16.2 kg) compared with those who had normal glucose tolerance (65.3 ± 14.5 kg; p < 0.05). In addition, triglycerides were higher in mothers with glucose intolerance (181.3 ± 85.9 mg/dl in IFG/IGT and 230.9 ± 90.9 mg/dl in diabetes) than in women with normal glycemia (147.8 ± 11.2 mg/dl; p < 0.05). CONCLUSION: We demonstrated an increased incidence of women exhibiting glucose intolerance within 1 year postpartum, mainly in those who remained obese.

Gene variants in the FTO gene are associated with adiponectin and TNF-alpha levels in gestational diabetes mellitus.

BACKGROUND: Obesity may have a role in the development of gestational diabetes mellitus (GDM). Single-nucleotide-polymorphisms (SNPs) of the FTO (fat mass and obesity associated) gene have been associated with obesity. The aim of this study was to investigate SNPs rs8050136, rs9939609, and rs1421085 of the FTO gene in women with GDM and their associations with maternal pre-pregnancy weight and body mass index, gestational weight gain and mediators of insulin resistance in GDM like leptin, adiponectin, ghrelin and tumor necrosis factor-alpha (TNF-alpha), compared with healthy pregnant controls. METHODS: 80 women with GDM and 80 women with normal pregnancy were considered for the present study. Genotyping of selected SNPs in all study subjects was done using the Taq-Man assay and the adipokines and ghrelin were measured by immunoassays. Chi square test, odds ratios (OR) and their respective 95% confidence intervals were used to measure the strength of association between FTO SNPs and GDM. RESULTS: There was no association among FTO SNPs and GDM. Interestingly, in GDM group, women carrying the risk alleles of the three SNPs had increased TNF-alpha, and decreased adiponectin levels; these associations remained significant after adjusting for pre-gestational body weight and age. Moreover, the risk allele of rs1421085 was also associated with increased weight gain during pregnancy. CONCLUSIONS: The FTP SNPs rs8050136, rs9939609, and rs1421085 are not a major genetic regulator in the etiology of GDM in the studied ethnic group. However, these SNPs were associated with adiponectin and TNF-alpha concentrations in GDM subjects.

RBP4 gene variants are associated with insulin resistance in women with previous gestational diabetes.

OBJECTIVE: This study aimed to examine possible genetic effects of some retinol binding protein-4 (RBP4) single nucleotide polymorphisms (SNPs) on the risk of gestational diabetes mellitus (GDM). In addition, the SNPs were examined for their possible association with insulin resistance at 6 weeks after delivery. METHODS: This was a prospective study of 100 women with GDM and 100 participants with normal gestation who were evaluated at gestational week 30 and 6 weeks postpartum. Three SNPs of RBP4 (rs3758539, rs116736522, and rs34571439) were genotyped using TaqMan assay. The genotype distributions between GDM patients and normal controls were analyzed using logistic regression models. In addition, differences in clinical characteristics among subjects grouped by genotype were assessed using the analysis of covariance test. RESULTS: The frequencies of the rare alleles were not significantly different between GDM patients and controls. However, we identified two variants rs3758539 and rs34571439 associated with insulin levels and insulin resistance in women with previous GDM. CONCLUSION: Noncoding SNPs of the RBP4 gene are not associated with GDM, but two SNPs showed associations with insulin resistance and insulin levels in women with prior GDM. Additional studies with increased sample size will be necessary in other GDM cohorts.

Relationship between circulating adipokines and insulin resistance during pregnancy and postpartum in women with gestational diabetes.

BACKGROUND AND AIMS: We undertook this study to assess the relationship between circulating adipokines and insulin resistance during pregnancy and postpartum in women with gestational diabetes mellitus (GDM). METHODS: This was a prospective study including 60 women with GDM and 60 subjects with normal gestation who were evaluated at gestational week 30, 6 weeks and 6 months postpartum. Circulating adipokines that were evaluated during the study were leptin, adiponectin, retinol-binding protein-4 (RBP4), and tumor necrosis factor-alpha (TNF-α). RESULTS: Women with GDM showed higher insulin resistance measured by HOMA-IR than subjects with normal gestation (2.3 ± 2.3 vs. 1.3 ± 0.95). There was no difference between groups in adipokines; however, in women with a healthy pregnancy, RBP4 was associated with insulin resistance (r = 0.47, p <0.05). At 6 weeks and 6 months postpartum, women with previous GDM exhibited persistent elevated leptin and insulin resistance. RBP4 was associated with insulin resistance only in women with a previous healthy pregnancy (r = 0.51, p <0.05). In addition, progressively impaired glucose tolerance was observed after delivery in women with previous GDM. CONCLUSIONS: It was demonstrated that GDM is associated with greater insulin resistance than observed in normal pregnancy; however, adipokines are similar in both groups. RBP4 levels are significantly associated with insulin resistance in healthy women during pregnancy and postpartum. After a pregnancy complicated by GDM, leptin and insulin resistance remain elevated and glucose tolerance worsens.

La lactancia prolongada se relaciona con menores niveles de leptina en pacientes con diabetes mellitus gestacional / Duration of lactation is associated with lower leptin levels in patients with gestational diabetes mellitus

Las mujeres con diabetes mellitus gestacional (DBTG) tienen un riesgo elevado de presentar diabetes tipo 2 en el posparto. La lactancia materna se ha asociado con una disminución del riesgo de diversas enfermedades metabólicas. El objetivo de este estudio fue evaluar el impacto de la duración de la lactancia sobre niveles de leptina en mujeres con DBTG previa, en comparación con mujeres con embarazo normal. Materiales y métodos: Se realizó un análisis secundario a una base de datos de un estudio prospectivo comparativo en el que se evaluaron en el embarazo y el posparto 43 mujeres con DBTG y 43 embarazadas normotensas euglucémicas. Se clasificó a las participantes de acuerdo con el tiempo de lactancia materna en duración breve (menos de 6 semanas) o duración prolongada (más de 6 semanas a menos de 6 meses) y se determinaron sus niveles de leptina. Resultados: Las mujeres con DBTG que tuvieron una lactancia de duración prolongada presentaron una mayor disminución de peso en el posparto y un menor nivel de leptina, en comparación con las de lactancia materna de duración breve. Esta diferencia permaneció estadísticamente significativa después del ajuste por el peso de las participantes. En el grupo de control, las mujeres con lactancia de duración prolongada presentaron menores niveles de triglicéridos, insulina y resistencia a la insulina. Conclusiones: La duración prolongada de la lactancia se asoció con menores niveles de leptina y con mejor perfil metabólico en el período posparto temprano de las mujeres con DBTG previa y con embarazo normal, respectivamente...