Renata Saucedo

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.

Adiponectin is associated with low bone mineral density in elderly men

OBJECTIVE Recent evidence suggests that adiponectin may play a role in bone metabolism. Previous studies demonstrated that the adiponectin levels had a negative correlation with bone mineral density (BMD) in women. However, little is known about the relationship between adiponectin and BMD in men. The aim of this study was to determinate the relationship between the adiponectin levels and BMD in elderly men. DESIGN Cross-sectional study including 92 healthy men aged 60-80 years. METHODS Main outcome measures were the adiponectin levels estimated by RIA and BMD at lumbar spine and femoral neck using dual energy X-ray absorptiometry. Results The negative correlation between adiponectin and BMD at the spine was r=-0.209, (P<0.05) and at the femoral neck was r=-0.237, (P<0.001). These correlations disappeared after adjustment for body mass index (BMI). When stratified by BMI, the relationship between BMD and adiponectin remained significant in the subgroup of participants with BMI >27 kg/m(2), but disappeared in men with BMI <or=27 kg/m(2). In multiple regression analysis, adiponectin was a significant determinant of BMD at the spine, not at the femoral neck, in those with BMI >27. CONCLUSION BMD is negatively associated with the adiponectin levels in men older than 60 years and this relationship is greater in those men with BMI >27, which suggests a plausible connection between bone and fat tissue.

Transdermal estradiol in menopausal women depresses interleukin-6 without affecting other markers of immune response

Objective: The aim of this study was to analyze the effect of transdermal estradiol replacement therapy (HRT) on immune function in menopausal women. Study Design: A prospective comparative study was carried out in 30 women, aged 48–55 years, who were divided into two groups; 20 of them received transdermal estradiol 50 µg/day during 3 months and 10 who refused to receive HRT served as controls. Serum interleukins were quantified by specific immunoenzymatic assays; in addition, hormones of somatotropin axis and prolactin (PRL) were quantified by IRMA and RIA. Results: Baseline elevated interleukin (IL)-6 levels decreased significantly (p < 0.001) after transdermal HRT as compared with the nontreated group. Contrarily, IL-2 and IL-10 levels as well as mitogenic induced T-cell proliferation were unchanged under HRT. Insulin-like growth factor-I, growth hormone and PRL levels were unaltered by transdermal HRT. Conclusion: Decrement of IL-6 in parallel with absent effect on some indices of immune activity suggests a beneficial action of transdermal HRT. These findings contrast with those demonstrating an increment of immune response in women taking oral HRT. Thus, the route of administra tion determines the effect of HRT on immune function.

Effect of testosterone therapy on lumbar spine and hip mineral density in elderly men

Objective. The aim of the present study was to analyse the effect of testosterone therapy on bone mineral density in healthy elderly men who had low levels of total testosterone. Design. Randomized, double-blind, placebo-controlled study. Participants. Forty-eight men over 60 years old with decreased testosterone levels (≤320 ng/dL) comprised the study. Twenty-five out of 48 received intramuscular injections of testosterone enanthate every three weeks during 12 months; the remaining 23 participants formed the control group. All participants had measurements of bone mineral density (BMD) in both lumbar spine and hip before and at the end of the study as well as testosterone and 17-β estradiol levels. Results: Testosterone treated group exhibited a significant (p < 0.05) increment (from 1.198 ± 0.153 to 1.240 ± 0.141 g/cm2) in lumbar BMD in parallel with a significant (p < 0.001) increment (from 301 ± 32 to 471 ± 107 ng/dL) in testosterone concentrations, whereas no significant change occurred in femoral neck BMD. Conclusions. Testosterone therapy elicited a positive effect only in lumbar BMD in elderly men with diminished testosterone serum levels.

Early Disturbed Placental Ischemia and Hypoxia Creates Immune Alteration and Vascular Disorder Causing Preeclampsia

Preterm preeclampsia (PE) remains a leading cause of maternal death and perinatal morbidity. The pathophysiological process that underlies PE has been proposed to occur in two episodes, the first is a reduced placental perfusion and then the maternal clinical syndrome. Placental ischemia/hypoxia is believed to result in the release of a variety of placental factors such as cytokines including TNF-α and interleukin 6, activated circulating immune cells and autoantibodies that have profound effects on blood flow and arterial pressure regulation. PE is also associated with decreased formation of vasodilators such as nitric oxide and prostacyclin. It is accompanied by widespread maternal vascular dysfunction and a chronic inflammatory response. Additionally, anti-angiogenic peptides are released, inhibiting vascular remodeling essential for increased blood flow to the growing uteroplacental unit. Although these factors accompany the clinical syndrome of PE, it is suggested that they are secondary to the maternal decrease in placental blood flow. Experimental evidence has demonstrated the importance of these soluble factors to increase blood pressure and stimulate the production of such anti-angiogenic factors, thereby eliciting a vicious cycle existing within the maternal vasculature as well as within the placental unit. These alterations in vascular function not only lead to hypertension but to multi-organ dysfunction. The quantitative importance of the various endothelial and humoral factors that mediate vascular dysfunction and hypertension during PE remains to be elucidated.

Oxidative Stress Changes in Pregnant Patients With and Without Severe Preeclampsia

BACKGROUND AND AIMS The etiology of preeclampsia (PE) is unknown and the only treatment is removal of the fetus and placenta. The critical changes of this state include the increase of vascular resistance and hypoperfusion in the uteroplacental microcirculation that predispose to hypoxia and ischemia and, therefore, increased oxidative stress through 8-isoprostane, which is characterized by damage to the placenta and endothelium. We undertook this study to compare oxidative stress in pregnant women with PE. METHODS A case-control, cross-sectional and comparative study was undertaken. Pregnant women between 28 and 38 weeks of gestation with and without PE were recruited. Venous blood samples were taken for determination of 8-isoprostane. Obstetrical variables were measured and 8-isoprostane by radioimmunoassay. SPSS v.11 for Windows was used for descriptive statistics. Mean ± standard deviation, correlation and χ(2) were used for comparison between groups. RESULTS We studied 45 patients: 20 with PE (44.6%) and 25 without PE (55.4%). The average for 8-isoprostane in preeclamptic patients was 699.2 ± 38.6 pg/dl and without PE was 113.9 ± 52.4 pg/dL (p <0.01), gestational age 32.1 ± 2.6 and 35.1 ± 1.8 weeks, birth weight 1880 ± 238 g and 2787 ± 312 g, respectively. Apgar at birth was similar in both groups. CONCLUSIONS We found statistical differences in the 8-isoprostane levels in both groups. There was no correlation in perinatal results in both groups according to 8-isoprostane levels. These results could be the basis for the use of antioxidants in the management of PE to counteract tissue damage.

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.

Effect of Pulsed Estrogen Therapy on Hemostatic Markers in Comparison with Oral Estrogen Regimen in Postmenopausal Women

Background/Aims: Hormone replacement therapy (HRT) is associated with an increased risk of thromboembolism dependent on the type of HRT; therefore, we compared therapy effects of intranasal with oral estrogens on coagulation and fibrinolysis markers in postmenopausal women. Methods: A randomized study in which 29 healthy hysterectomized women received intranasal 17β-estradiol or oral estrogens for 3 months. Results: There were no significant differences in the baseline characteristics between groups. Those women receiving intranasal estradiol showed a mild increment in plasminogen activator inhibitor-1 (PAI-I) (from 6.8 ± 3.5 to 9.6 ± 3.9 U/ml, p < 0.01); however, fibrinogen, factor VII-tissue factor complex (VIIa-rTF), antithrombin III (ATIII), protein C (PC) activity, protein S (PS) activity, plasminogen (PLG), and tissue-type plasminogen activator antigen (t-PA) were unchanged. In contrast, oral unopposed estrogens elevated t-PA (from 4.9 ± 2.9 to 9.6 ± 5.1 ng/ml, p < 0.01) in parallel with a decrement in PAI-I (from 5.2 ± 4.0 to 2.7 ± 1.7 U/ml, p < 0.05) and VIIa-rTF (from 201.2 ± 181.0 to 140.6 ± 108.7 mU/ml, p < 0.05). Fibrinogen, ATIII, PC, PS, and PLG were unchanged. Conclusions: Nasal 17β-estradiol had no effect on the coagulation markers, except a moderate increment in PAI-1. In contrast, oral estrogens elicited a decrement in both VIIa-rTF and PAI-1; however, those changes did not surpass normal limits.

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

BackgroundObesity 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.Methods80 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.ResultsThere 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.ConclusionsThe 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.