Unfavorable cytokine and adhesion molecule profiles during and after pregnancy, in women with gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus is a significant risk factor for metabolic syndrome and cardiovascular disease. AIMS: To assess the relationships between components of the metabolic syndrome and cytokine and adhesion molecule levels in women with GDM during pregnancy and after delivery. PATIENTS AND METHODS: A prospective case-control study on a sample of 126 pregnant women (63 with and 63 without gestational diabetes mellitus). In an intra-subject analysis, 41 women with history of gestational diabetes mellitus and 21 controls were re-assessed in the postpartum period. Clinical data and levels of cytokines and adhesion molecules were recorded during weeks 24-29 of pregnancy and 12 months after delivery. RESULTS: In the postpartum period, there were significantly higher levels of tumor necrosis factor alpha in both cases and controls, and of adiponectin in controls. Cases showed higher leptin levels, with no significant differences during and after pregnancy. No significant differences were seen in adhesion molecules and interleukin-6 between cases and controls during pregnancy and in the postpartum period, but levels of both were higher in cases. During pregnancy and after delivery, adiponectin decreased in cases and increased in controls. Significant positive correlations were seen between adiponectin and fasting blood glucose levels and vascular cell adhesion molecule-1, and also between leptin and tumor necrosis factor alpha levels. CONCLUSIONS: The results suggest that increased inflammation and transient hyperglycemia during pregnancy would represent a latent form of metabolic syndrome, with an increased risk for type 2 diabetes mellitus and future cardiovascular disease.

Unfavorable cytokine and adhesion molecule profiles during and after pregnancy, in women with gestational diabetes mellitus / Perfiles de citocinas y moléculas de adhesión desfavorables durante y después del embarazo en mujeres con diabetes mellitus gestacional

Background: Gestational diabetes mellitus is a significant risk factor for metabolic syndrome and cardiovascular disease. Aims: To assess the relationships between components of the metabolic syndrome and cytokine and adhesion molecule levels in women with GDM during pregnancy and after delivery. Patients and methods: A prospective case-control study on a sample of 126 pregnant women (63 with and 63 without gestational diabetes mellitus). In an intra-subject analysis, 41 women with history of gestational diabetes mellitus and 21 controls were re-assessed in the postpartum period. Clinical data and levels of cytokines and adhesion molecules were recorded during weeks 24-29 of pregnancy and 12 months after delivery. Results: In the postpartum period, there were significantly higher levels of tumor necrosis factor alpha in both cases and controls, and of adiponectin in controls. Cases showed higher leptin levels, with no significant differences during and after pregnancy. No significant differences were seen in adhesion molecules and interleukin-6 between cases and controls during pregnancy and in the postpartum period, but levels of both were higher in cases. During pregnancy and after delivery, adiponectin decreased in cases and increased in controls. Significant positive correlations were seen between adiponectin and fasting blood glucose levels and vascular cell adhesion molecule-1, and also between leptin and tumor necrosis factor alpha levels. Conclusions: The results suggest that increased inflammation and transient hyperglycemia during pregnancy would represent a latent form of metabolic syndrome, with an increased risk for type 2 diabetes mellitus and future cardiovascular disease (AU)

Antecedentes: La diabetes mellitus gestacional es un factor de riesgo importante para el síndrome metabólico y la enfermedad cardiovascular. Objetivos: Se evaluaron las relaciones entre los componentes del síndrome metabólico, los niveles de citocinas y moléculas de adhesión en mujeres con diabetes gestacional durante el embarazo y en el posparto. Pacientes y métodos: Estudio prospectivo de casos y controles. Se analizaron 126 mujeres gestantes (63 con diabetes mellitus gestacional y 63 controles). En el periodo posparto, se reevaluaron 41 casos y 21 controles. Se analizaron variables clínicas, niveles de citocinas y moléculas de adhesión durante las semanas 24-29 de la gestación y 12 meses después del parto. Resultados: En el periodo posparto, el factor de necrosis tumoral alfa en casos y controles, y la adiponectina en controles fueron significativamente más altos. Los casos mostraron mayores niveles de leptina, sin diferencias significativas durante el embarazo y después del parto. No se observaron diferencias significativas en las moléculas de adhesión y la interleucina 6 entre casos y controles durante el periodo de embarazo y el posparto, pero ambos fueron mayores en los casos. Durante el embarazo y posparto, la adiponectina disminuyó en los casos y aumentó en los controles. Observamos correlaciones positivas significativas entre adiponectina con glucemia en ayunas y moléculas de adhesión celular vascular-1, y entre leptina y factor de necrosis tumoral alfa. Conclusiones: Los resultados indican que el aumento de la inflamación y la hiperglucemia transitoria durante el embarazo representarían una forma latente de síndrome metabólico, con un mayor riesgo de diabetes mellitus tipo 2 y de enfermedad cardiovascular en el futuro (AU)

Tissue specific expression of human fatty acid oxidation enzyme genes in late pregnancy.

BACKGROUND: Abnormal fatty acid oxidation (FAO) is associated with maternal and fetal complications during pregnancy. The contribution of maternal and fetal tissues to FAO capacity during late pregnancy is important to understand the pathophysiology of pregnancy-associated complications. The aim of this study was to determine the expression levels of mitochondrial FAO enzymes in maternal and fetal tissues during late normal pregnancy. METHODS: We have measured by Real-time PCR the levels of long- and medium -chain acyl-CoA dehydrogenase (LCHAD and MCAD), two acyl-CoA dehydrogenases that catalyze the initial step in the mitochondrial FAO spiral. RESULTS: LCHAD and MCAD were expressed in maternal skeletal muscle, subcutaneous adipose tissue, placenta, and maternal and fetal blood cells. LCHAD gene expression was four- to 16-fold higher than MCAD gene expression in placenta, adipose tissue and skeletal muscle. In contrast, MCAD gene expression was ~5-fold higher in fetal blood than maternal blood (p = 0.02), whereas LCHAD gene expression was similar between fetal blood and maternal blood (p =0.91). CONCLUSIONS: LCHAD and MCAD are differentially expressed in maternal and fetal tissues during normal late pregnancy, which may represent a metabolic adaptation in response to physiological maternal dyslipidemia during late pregnancy.

Adipokines and metabolic syndrome risk factors in women with previous gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) has been recognized as a significant risk factor for metabolic syndrome and CVD. The aim of the study was to evaluate the relationships between levels of cytokines, components of metabolic syndrome and cardiovascular risk markers in women with previous gestational diabetes. METHODS: Women (n = 41) with gestational diabetes background (cases) and 21 healthy women (controls) in the postpartum period were enrolled. Demographic and clinical data, lipid and carbohydrate metabolism and uric acid and adipokine levels (TNF-α, IL-6, leptin and adiponectin) were compared and their relationships analysed. Metabolic syndrome prevalence was calculated by WHO and NCEP-ATPIII definitions. RESULTS: There were significant differences between cases and controls: body mass index (kg/m(2) ) 27.4 ± 5.6 vs 23.9 ± 3.6 (p = 0.013), waist circumference (cm) 85.2 ± 12.9 vs 77.5 ± 9.0 (p = 0.017), metabolic syndrome (WHO definition) 14.6% vs 0% (p = 0.012), metabolic syndrome (NCEP-ATPIII definition) 22% vs 0% (p = 0.002), low HDL 36.6% vs 9.5% (p = 0.024), fasting glucose (mmol/L) 5.4 ± 0.6 vs 4.9 ± 0.2 (p < 0.001), glucose 120' oral glucose tolerance test (mmol/L) 5.8 ± 1.7vs 4.7 ± 0.8 (p = 0.007), fasting insulin (µU/mL) 13.4 ± 8.1 vs 8.4 ± 4.3 (p = 0.004), HOMA index 3.3 ± 2.3 vs 1.8 ± 1.0 (p = 0.002), HbA(1c) (%) 5.4 ± 0.2 vs 5.2 ± 0.2 (p = 0.021), uric acid (mg/dL) 4.1 ± 1 vs 3.5 ± 0.6 (p = 0.009), leptin (ng/mL) 32 025.5 ± 19 917.3 vs 20 258.9 ± 16 359.9 (p = 0.023), respectively. CONCLUSIONS: Women with previous gestational diabetes have central adiposity, atherogenic lipid profile, carbohydrate intolerance and adverse adipokine profile, all of which are risk factors for the future development of metabolic disease and CVD.

Inflammation and cardiovascular risk in women with preterm labor.

BACKGROUND: Women with a history of preterm delivery have about twice the normal risk of cardiovascular disease (CVD). Mechanisms underlying this association are not well understood. The aim of the present study was to evaluate the relationships between selected metabolic CVD risk factors and markers of both systemic inflammation and endothelial dysfunction in women with spontaneous preterm labor (sPL). METHODS: This was a case-control study in a university tertiary referral center. Forty pregnant women with sPL were compared to 50 controls during gestation. Maternal serum triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, glycemia, insulinemia, homeostasis model assessment (HOMA), leptin, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM), selectin, and myeloperoxidase (MPO) were measured. RESULTS: Gestational age at study was similar in both groups (31.56±3.14 weeks of gestation vs. 31.27±2.14 weeks of gestation, p=0.62, for the control and the sPL groups, respectively). Body mass index (BMI) (21.72±2.99 vs. 23.56±3.80, p=0.01), all cholesterol fractions (HDL-C 53.44±18.22 vs. 68.32±18.38, p=0.0003; LDL-C 125.71±35.56 vs. 142.15±36.07, p=0.03, and total cholesterol 219.55±32.29 vs. 240.38±40.01, p=0.009) and MPO (3.07±0.63 vs. 3.48±0.32, p=0.0009) were significantly lower in women with sPL. Serum levels of IL-6 (0.61±0.46 vs. 0.33±0.46, p=0.007) and the ratio of total cholesterol/HDL-C (4.52±1.48 vs. 3.77±1.37, p=0.01) were significantly increased and correlated each other (r=0.21, p=0.04). Logistic regression showed that the best predictive model for sPL (R(2)=0.36, p=0.001) included BMI and total cholesterol. CONCLUSIONS: A combination of low maternal BMI, low cholesterol levels, and high total cholesterol/HDL-C ratio is present in women with sPL and is related to inflammation.

Second-trimester amniotic fluid proinflammatory cytokine levels in normal and overweight women.

OBJECTIVE: To estimate the relationship between different adipokines and proinflammatory mediators in amniotic fluid and maternal body mass index (BMI), calculated as weight (kg)/height (m)2. METHODS: Seventy pregnant women who underwent amniocentesis for clinical reasons at 15-20 weeks of gestation were divided into two groups according to their BMI: a control group with normal weight (BMI 20-24.9, n=35) and a case group (BMI 25 or higher, n=35). The two groups were further divided into two subgroups: overweight (BMI 25-29.9, n=22) or obese (BMI 30 or more, n=13). Comparisons of amniotic fluid cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-8, IL-10, monocyte chemoattractant protein-1, resistin, and leptin) and C-reactive protein (CRP) levels were performed. The relationships between variables and maternal BMI were also analyzed. RESULTS: There were significant differences in amniotic fluid CRP and TNF-alpha levels among the studied groups: CRP, 0.018 (+/-0.010), 0.019 (+/-0.013), and 0.035 (+/-0.028) mg/dL (P=.007); and TNF-alpha, 3.98 (+/-1.63), 3.53 (+/-1.38), and 5.46 (+/-1.69) pg/mL (P=.003), for lean, overweight, and obese women, respectively. Both proinflammatory mediators increased in women with obesity compared with both overweight and normal women (P=.01 and P=.008 for CRP; P=.003 and P=.01 for TNF-alpha, respectively). There were significant correlations between maternal BMI and amniotic fluid CRP (r=0.396; P=.001), TNF-alpha (r=0.357; P=.003) and resistin (r=0.353; P=.003). CONCLUSION: Amniotic fluid CRP and TNF-alpha levels are increased in obese women, and both are related to maternal BMI, which suggests in utero exposure to higher proinflammatory cytokines and mediators in fetuses of these women. LEVEL OF EVIDENCE: II.

Transformed alpha-fetoprotein (t-AFP) levels in women with threatened preterm labor.

BACKGROUND/AIMS: To evaluate maternal serum transformed alpha-fetoprotein (MSt-AFP) levels, a new molecular conformation of AFP was used in cases of threatened preterm labor (TPL). METHODS: Prospective case-control study. Maternal serum levels of classical AFP and transformed AFP (t-AFP) were compared between 2 groups matched by gestational age: 25 women with TPL and 25 healthy pregnant women as controls. RESULTS: There was no significant difference in classical maternal serum AFP (MSAFP) levels between the 2 groups. In contrast, MSt-AFP levels were significantly lower in cases of TPL than in the control group [7.64 (1.78-29.06) vs. 33.38 (13.80-190.50) ng/ml; p = 0.006]. Similarly, the t-AFP:AFP ratio was also decreased in the TPL group [0.04 (0.004-0.12) vs. 0.16 (0.05-0.80); p = 0.008]. There was no significant correlation between MSAFP and MSt-AFP levels. CONCLUSIONS: MSt-AFP levels are decreased in women with TPL.