Significance of Umbilical Cord Leptin Profile during Pregnancy in Gestational Diabetes Mellitus-A Systematic Review and Meta-Analysis.

BACKGROUND: The literature provides limited evidence of cord blood leptin levels in gestational diabetes mellitus (GDM), with contradictory and inconsistent results with respect to their possible implications for maternal, perinatal, and future complications. METHODS: MEDLINE/PubMed, Embase, Scopus, and Web of Science databases were searched in order to investigate the state of evidence on the association of leptin profile in cord blood during perinatal complications in GDM. We critically assessed the risk of bias using the Newcastle-Ottawa scale. Meta-analyses were performed, and heterogeneity and publication bias were analyzed. RESULTS: sixteen primary-level studies were included, recruiting 573 GDM and 1118 control pregnant women. Cord blood leptin levels were significantly higher in GDM participants compared to controls (standardized mean difference [SMD] = 0.59, 95% confidence intervals (CI) = 0.37 to 0.80, p < 0.001). All subgroups also maintained significant differences stratified by continents (Asia: SMD = 0.91, 95% CI = 0.45 to 1.37, p < 0.001; Europe: SMD = 0.38, 95% CI = 0.20 to 0.56, p < 0.001), analysis technique (ELISA: SMD = 0.70, 95% CI = 0.44 to 0.97, p < 0.001; RIA: SMD = 0.30, 95% CI = 0.11 to 0.49, p = 0.002), and sample source (plasma: SMD = 0.71, 95% CI = 0.33 to 1.09, p < 0.001; serum: SMD = 0.55, 95% CI = 0.34 to 0.77, p < 0.001). CONCLUSION: Cord blood leptin levels were significantly higher in GDM compared to controls. Further research is needed to clarify its role as a predictive biomarker of subsequent metabolic diseases in mothers with GDM and offspring.

Significance of cell adhesion molecules profile during pregnancy in gestational diabetes mellitus. A systematic review and meta-analysis.

Endothelial dysfunction has been considered as a key etiological factor contributed to the development of vascular disease in diabetes mellitus. Serum level of endothelial cell adhesion molecules (AMs) were reported to be increased in GDM and pregnant women with normal glucose tolerance when compared with nonpregnant women. The literature provides limited evidence of endothelial dysfunction in GDM with heterogeneous and contradictory results respect to their possible involvement in maternal, perinatal and future complications. Our objective is to evaluate current evidence on the role of AMs in maternal and perinatal complications in women with GDM. PubMed, Embase, Web of Science, and Scopus databases were searched. We evaluated the studies' quality using the Newcastle-Ottawa scale. Meta-analyses were conducted, and heterogeneity and publication bias were examined. Nineteen relevant studies were finally included, recruiting 765 GDM and 2368 control pregnant women. AMs levels were generally higher in GDM participants showing statistical significance maternal ICAM-1 levels (SMD = 0.58, 95% CI = 0.25 to 0.91; p = 0.001). Our meta-analysis did not detect significant differences in subgroups or in meta-regression analyses. Future studies are needed to establish the potential role of these biomarkers in GDM and its complications.

Higher daytime systolic BP, prepregnancy BMI and an elevated sFlt-1/PlGF ratio predict the development of hypertension in normotensive pregnant women.

BACKGROUND: The risk of hypertensive disorders of pregnancy (HDP) varies in women with gestational diabetes mellitus (GDM), depending on the degree of insulin resistance and is also influenced by obesity. The aim of this study was to evaluate clinical features, blood pressure (BP) profiles and inflammatory markers, to identify patients with an elevated risk of developing HDP. METHODS: A total of 146 normotensive pregnant women were studied. We analysed the relationships of BP profiles detected by ambulatory blood pressure monitoring (ABPM) with serum biomarkers and angiogenic factors and their association with the development of HDP. RESULTS: Fourteen (9.6%) women developed HDP, of which 11 had GDM and 8 had obesity. Women with HDP had higher values of 24-h and daytime systolic/diastolic BP (113/69 vs. 104/64; 115/72 vs. 106/66 mmHg, respectively; p <  0.05). Higher levels of leptin (10.97 ± 0.82 vs. 10.2 ± 1.11; p = 0.018) andmonocyte chemoattractant protein-1 (MCP-1) (5.24 ± 0.60 vs. 4.9 ± 0.55; p = 0.044) and a higher soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio (4.37 ± 2.2 vs. 2.2 ± 1.43; p = 0.003) were also observed in the HDP patients. Multivariate analysis showed that a higher sFlt-1/PlGF ratio was associated with an increased risk of developing HDP [OR = 2.02; IC 95%: 1.35-3.05]. Furthermore, higher daytime systolic BP [OR = 1.27; IC 95% 1.00-1.26] and prepregnancy body mass index (BMI) [OR = 1.14; IC 95%: 1.01-1.30] significantly increased the risk of developing HDP. CONCLUSIONS: Higher daytime systolic BP values, prepregnancy BMI and the sFlt-1/PlGF ratio are useful for identifying normotensive pregnant women with an increased risk of developing HDP.

Significance of Serum-Plasma Leptin Profile during Pregnancy in Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Gestational diabetes mellitus (GDM) represents a stage of subclinical inflammation and a risk factor for subsequent future type 2 diabetes and cardiovascular disease development. Leptin has been related with vascular and metabolic changes in GDM with heterogeneous and contradictory results with respect to their possible involvement in maternal, perinatal, and future complications. Our objective is to evaluate current evidence on the role of leptin in maternal and perinatal complications in women with GDM. PubMed, Embase, Web of Science, and Scopus databases were searched. We evaluated the studies' quality using the Newcastle-Ottawa scale. Meta-analyses were conducted, and heterogeneity and publication bias were examined. Thirty-nine relevant studies were finally included, recruiting 2255 GDM and 3846 control pregnant women. Leptin levels were significantly higher in GDM participants than in controls (SMD = 0.57, 95%CI = 0.19 to 0.94; p < 0.001). Subgroup meta-analysis did not evidence significant differences in leptin in the different trimesters of pregnancy. Meta-regression showed a positive significant relationship for HOMA in the GDM group (p = 0.05). According to these results, it seems that high levels of leptin can be used as predictive markers in GDM.

Fetal cerebral three-dimensional power Doppler vascularization indices and their relationships with maternal glucose levels in pregnancies complicated with gestational diabetes.

OBJECTIVES: We aimed to evaluate fetal cerebral circulation using three-dimensional power Doppler (3DPD) vascular indices and to study their relationships with maternal lipid and glycaemic profiles. METHODS: Case-control study in women with and without gestational diabetes mellitus (GDM) at 28-32 weeks in which feto-maternal Doppler study and 3DPD cerebral vascularization indices (FI, VI and VFI) were determined. Maternal lipid and glycaemic profiles were also analysed. Both groups were compared and the correlations of the 3DPD indices with studied variables were analysed. RESULTS: There were significant differences between groups in cerebral FI (p= 0.02), mean maternal Uterine artery PI (p= 0.009) and glucose levels (p= 0.001), being higher in the GDM group. Significant negative correlations were found in GDM group between VFI and MCA PI (p = 0.02) and between VI and MCA PI (p= 0.01). In the GDM group we found a negative significant correlation between FI, VI, VFI and maternal glucose (r= -0.52, p<0.001; r= -0.32, p=0.03 and r= -0.36, p= 0.01, respectively). CONCLUSIONS: Fetal cerebral FI values were higher in GDM pregnancies. All 3DPD vascular indices showed an inverse correlation with maternal glucose levels. These findings support the view that GDM may also represent a fetal vascular disorder influencing fetal neurodevelopment.

Blood Pressure Monitoring and Perinatal Outcomes in Normotensive Women with Gestational Diabetes Mellitus.

Alterations in ambulatory blood pressure detected by monitoring (ABPM) have been associated with perinatal complications in hypertensive pregnant women. AIM: To establish the relationships between the blood pressure (BP) profiles detected by ABPM and adverse perinatal outcomes in normotensive women with gestational diabetes mellitus (GDM). METHODS: A prospective study of normotensive women in whom 24 h ABPM was performed at 28-32 weeks of pregnancy. The obstetric and perinatal outcomes were evaluated. RESULTS: Two hundred patients were included. Thirty-seven women with GDM and obesity had significantly higher mean systolic BP (SBP) and nocturnal SBP and diastolic BP (DBP) compared to women with only GDM (n = 86). Nocturnal SBP (OR = 1.077; p = 0.015) and obesity (OR = 1.131; p = 0.035) were risk factors for the development of hypertensive disorders of pregnancy (HDPs). Mothers of newborns with neonatal complications (n = 27) had higher nocturnal SBP (103.8 vs. 100 mmHg; p = 0.047) and DBP (62.7 vs. 59.4; p = 0.016). Women who delivered preterm (n = 10) had higher BP and a non-dipper pattern (p = 0.005). CONCLUSIONS: Nocturnal SBP was a predictor of HDPs in normotensive women with obesity or GDM. Alterations in ABPM in these patients were associated with poor obstetric and perinatal outcomes.

Angiogenic Imbalance and Inflammatory Biomarkers in the Prediction of Hypertension as Well as Obstetric and Perinatal Complications in Women with Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) increases the risk of hypertensive disorders of pregnancy (HDP). We aimed to analyze the altered inflammatory markers and angiogenic factors among women with GDM to identify pregnant women at higher risk of developing HDP. Methods: This was a prospective study of 149 women without hypertension diagnosed in the third trimester with GDM. Inflammatory markers and angiogenic factors were measured at 28−32 weeks of pregnancy. Obstetric and perinatal outcomes were evaluated. Results: More than eight percent of the women developed HDP. Higher levels of the soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PIGF) ratio (4.9 ± 2.6 versus 2.3 ± 1.3, respectively; p < 0.001) and leptin (10.9 ± 0.8 versus 10.08 ± 1.1, respectively; p = 0.038), as well as lower levels of adiponectin (10.5 ± 1.3 versus 12.9 ± 2.7, respectively; p = 0.031), were seen in women who developed HDP versus normotensive women with GDM. A multivariable logistic regression analysis showed that adiponectin had a protective effect with 0.45-fold odds (0.23−0.83; p = 0.012), and that the sFlt-1/PIGF ratio was associated with 2.70-fold odds of developing HDP (CI 95%: 1.24−5.86; p = 0.012). Conclusion: An increase in angiogenic imbalance in the sFlt-1/PIGF ratio in women with GDM was detected and may be an indicator of developing HDP in addition to any subsequent obstetric and perinatal complications.

Anti-Inflammatory (M2) Response Is Induced by a sp2-Iminosugar Glycolipid Sulfoxide in Diabetic Retinopathy.

Diabetic retinopathy (DR) is one of the most common complications of Diabetes Mellitus (DM) and is directly associated with inflammatory processes. Currently, neuro-inflammation is considered an early event in DR and proceeds via microglia polarization. A hallmark of DR is the presence of retinal reactive gliosis. Here we report the beneficial effect of (SS,1R)-1-docecylsulfiny-5N,6O-oxomethylidenenojirimycin ((Ss)-DS-ONJ), a member of the sp2-iminosugar glycolipid (sp2-IGL) family, by decreasing iNOS and inflammasome activation in Bv.2 microglial cells exposed to pro-inflammatory stimuli. Moreover, pretreatment with (Ss)-DS-ONJ increased Heme-oxygenase (HO)-1 as well as interleukin 10 (IL10) expression in LPS-stimulated microglial cells, thereby promoting M2 (anti-inflammatory) response by the induction of Arginase-1. The results strongly suggest that this is the likely molecular mechanism involved in the anti-inflammatory effects of (SS)-DS-ONJ in microglia. (SS)-DS-ONJ further reduced gliosis in retinal explants from type 1 diabetic BB rats, which is consistent with the enhanced M2 response. In conclusion, targeting microglia polarization dynamics in M2 status by compounds with anti-inflammatory activities offers promising therapeutic interventions at early stages of DR.

Evaluation of pregnancy outcomes in women with GCK-MODY.

AIMS: To determine the fetal and maternal outcomes in pregnant women with Glucokinase-Maturity onset diabetes of the young (GCK-MODY). METHODS: We studied the obstetric and perinatal outcomes in 99 pregnancies of 34 women with GCK-MODY. The mutation status of the offspring was known in 29 and presumed in 33. Clinical outcomes were determined and compared between affected (n = 39) and unaffected (n = 23) offspring. RESULTS: 59% of pregnancies were treated with diet alone and 41% received insulin. Birthweight, percentage of large for gestational age (LGA) and caesarean section (CS) in GCK-unaffected offspring was significantly higher than in GCK-affected offspring (4.0 ± 0.7 vs. 3.4 ± 0.4 kg, p = 0.001), 15 (65%) vs. 5(13%) (p = 0.00006) and 17 (74%) vs. 11 (28%) (p = 0.001), respectively. We observed an earlier gestational age at delivery on insulin in unaffected offspring (38.3 ± 1.0 vs. 39.5 ± 1.5 weeks, p = 0.03) with no significant change in LGA (9 (82%) vs. 6 (50%); p = 0.12), and a higher rate of CS (8 [73%] vs. 3 [11%]; p < 0.001), and no change in small for gestational age (0 [0%] vs. 4 [14%]; p = 0.30) in affected offspring. CONCLUSION: Insulin therapy in unaffected offspring did not reduce LGA and was associated with earlier gestational age at delivery. Insulin treatment in GCK-affected offspring was associated with an increased incidence of CS, but did not adversely affect fetal outcome. Fetal genotype determines birthweight rather than treatment. Pre-pregnancy diagnosis of GCK-MODY, use of continuous glucose monitoring and non-invasive fetal genotyping may enable further investigation of targeted therapy in this condition.

Circulating miR-330-3p in Late Pregnancy is Associated with Pregnancy Outcomes Among Lean Women with GDM.

Gestational Diabetes Mellitus (GDM) is characterised by insulin resistance accompanied by reduced beta-cell compensation to increased insulin demand, typically observed in the second and third trimester and associated with adverse pregnancy outcomes. There is a need for a biomarker that can accurately monitor status and predict outcome in GDM, reducing foetal-maternal morbidity and mortality risks. To this end, circulating microRNAs (miRNAs) present themselves as promising candidates, stably expressed in serum and known to play crucial roles in regulation of glucose metabolism. We analysed circulating miRNA profiles in a cohort of GDM patients (n = 31) and nondiabetic controls (n = 29) during the third trimester for miRNA associated with insulin-secretory defects and glucose homeostasis. We identified miR-330-3p as being significantly upregulated in lean women with GDM compared to nondiabetic controls. Furthermore, increased levels of miR-330-3p were associated with better response to treatment (diet vs. insulin), with lower levels associated with exogenous insulin requirement. We observed miR-330-3p to be significantly related to the percentage of caesarean deliveries, with miR-330-3p expression significantly higher in spontaneously delivered GDM patients. We report this strong novel association of circulating miR-330-3p with risk of primary caesarean delivery as a pregnancy outcome linked with poor maternal glycaemic control, strengthening the growing body of evidence for roles of diabetes-associated miRNAs in glucose homeostasis and adaptation to the complex changes related to pregnancy.

Effect of Different Insulin Therapies on Obstetric-Fetal Outcomes.

To evaluate the effectiveness of the different insulin therapies on obstetrics-fetal outcomes in women with pregestational diabetes mellitus. We enrolled 147 pregnant women with pre-existing type 1 or 2 diabetes mellitus. Clinical and biochemical parameters were analysed in relation to obstetric and fetal outcomes. 14.2% received treatment with Neutral Protamine Hagedorn insulin and short-acting insulin analogues; 19% with premixed human insulin; 40.1% with insulin glargine and lispro, 6.2% with detemir and aspart and 20% with continuous subcutaneous insulin infusion. All 5 types of treatment achieved a reduction of the mean HbA1c during pregnancy (p = 0.01). Pre-pregnancy care was carried out for 48% of patients. We found no statistically significant differences between the different insulin therapies and the obstetric-fetal outcomes. In conclusión, the different insulin therapies used in patients with pregestational diabetes mellitus does not seem to affect obstetric-fetal outcomes.

Utilidad de la monitorización ambulatoria de la presión arterial en mujeres con diabetes mellitus gestacional / Usefulness of blood pressure monitoring in patients with gestational diabetes mellitus

Antecedentes y objetivos: Las pacientes con diabetes mellitus gestacional (DMG) presentan un mayor riesgo de desarrollar hipertensión arterial inducida por el embarazo (HIE). La monitorización ambulatoria de presión arterial (MAPA) ha sido usada para detectar HIE y preeclampsia, pero hasta la fecha no ha sido suficientemente estudiada en DMG. El objetivo del presente trabajo es identificar de forma precoz, en mujeres con DMG, perfiles de presión arterial (PA), detectados mediante MAPA, que pudieran definir una población de mayor riesgo de desarrollar HIE y preeclampsia. Material y métodos: Estudio prospectivo en 93 pacientes con PA normal con DMG. Se les implantó entre la semana 28-32 de gestación la MAPA durante 24h (Spacelabs 90207) y se analizaron variables clínicas, analíticas y resultados obstétricos y perinatales. Resultados: La edad media fue 34,8±4,39años. Cinco pacientes (5,4%) desarrollaron HIE. Encontramos niveles más elevados de HbA1c (p=0,005) y microalbuminuria (p=0,001) entre las que desarrollaron HIE. Las pacientes con patrón no dipper (50,5%) presentaron cifras de PAS nocturna (106,7 vs 98,4mmHg) y PAD nocturna (64,8 vs 57,2mmHg) más elevadas (p<0,001). Se observó menor peso al nacimiento (3.084,57 vs 3.323,7; p=0,021) y menor semana de gestación en el momento del parto (38,67 vs 39,27 semanas; p=0,04) en pacientes con patrón no dipper respecto al dipper. La PAS nocturna elevada se asoció con un incremento significativo de la probabilidad de HIE (OR: 1,18; IC95%: 1,00-1,39; p=0,043). Conclusiones: En la DMG existen alteraciones tensionales con un predominio de patrón no dipper de PA y con valores más elevados de PAS y PAD nocturnos, pudiendo ser estas alteraciones predictoras de HIE. Los valores elevados de PAS nocturna aumentan el riesgo de desarrollo de HIE. Se requieren futuros estudios para determinar la relación entre las alteraciones tensionales y las complicaciones maternas y perinatales

Background and objective: Gestational diabetes mellitus (GDM) is associated to an increased risk of pregnancy-induced hypertension (PIH). Ambulatory blood pressure monitoring (ABPM) has been used to detect PIH and preeclampsia, but few data are currently available on its use in women with GDM. The aim of this study was to achieve early identification in women with GDM of BP profiles (detected by ABPM) that could define a population at greater risk of developing PIH and preeclampsia. Material and methods: A prospective study of 93 normotensive women with GDM in whom 24-h ABPM was performed (using a Spacelabs 90207 monitor) at 28-32 weeks of pregnancy. Clinical and laboratory variable and obstetric and perinatal outcomes were analyzed. Results: Mean age was 34.8±4.39years, and 5.4% of patients developed PIH. Higher levels of HbA1c (P=.005) and microalbumin (P=.001) were seen in patients with PIH. Patients with non-dipper patterns (50.5%) had higher values of night-time systolic BP (106.7 vs 98.4mmHg) and night-time diastolic BP (64.8 vs 57.2mmHg) (P<.001). Lower birth weights (3,084.57 vs 3,323.7) (P=.021) and shorter gestational age at delivery (38.67 vs 39.27 weeks) (P=.04) were found in women with non-dipper pattern. High night-time systolic BP significantly increased the chance of developing PIH (OR: 1.18; 95%CI: 1.00-1.39; P=.043). Conclusions: Patients with GDM have BP changes, with predominance of the non-dipper pattern and higher night-time systolic and diastolic BP, changes that could be useful predictors of PIH. High night-time systolic BP values increase the risk of developing PIH. Further studies are needed to ascertain the relationships between BP changes and obstetric and perinatal complications

Usefulness of blood pressure monitoring in patients with gestational diabetes mellitus. / Utilidad de la monitorización ambulatoria de la presión arterial en mujeres con diabetes mellitus gestacional.

BACKGROUND AND OBJECTIVE: Gestational diabetes mellitus (GDM) is associated to an increased risk of pregnancy-induced hypertension (PIH). Ambulatory blood pressure monitoring (ABPM) has been used to detect PIH and preeclampsia, but few data are currently available on its use in women with GDM. The aim of this study was to achieve early identification in women with GDM of BP profiles (detected by ABPM) that could define a population at greater risk of developing PIH and preeclampsia. MATERIAL AND METHODS: A prospective study of 93 normotensive women with GDM in whom 24-h ABPM was performed (using a Spacelabs 90207 monitor) at 28-32 weeks of pregnancy. Clinical and laboratory variable and obstetric and perinatal outcomes were analyzed. RESULTS: Mean age was 34.8±4.39years, and 5.4% of patients developed PIH. Higher levels of HbA1c (P=.005) and microalbumin (P=.001) were seen in patients with PIH. Patients with non-dipper patterns (50.5%) had higher values of night-time systolic BP (106.7 vs 98.4mmHg) and night-time diastolic BP (64.8 vs 57.2mmHg) (P<.001). Lower birth weights (3,084.57 vs 3,323.7) (P=.021) and shorter gestational age at delivery (38.67 vs 39.27 weeks) (P=.04) were found in women with non-dipper pattern. High night-time systolic BP significantly increased the chance of developing PIH (OR: 1.18; 95%CI: 1.00-1.39; P=.043). CONCLUSIONS: Patients with GDM have BP changes, with predominance of the non-dipper pattern and higher night-time systolic and diastolic BP, changes that could be useful predictors of PIH. High night-time systolic BP values increase the risk of developing PIH. Further studies are needed to ascertain the relationships between BP changes and obstetric and perinatal complications.

Impacto de la autoinmunidad antitiroidea positiva en gestantes con hipotiroidismo subclínico / Impact of positive thyroid autoimmunity on pregnant women with subclinical hypothyroidism

Introducción: El impacto del hipotiroidismo subclínico (HSC) y la autoinmunidad antitiroidea positiva en los resultados obstétricos y perinatales permanece en controversia y es objeto de gran interés. Objetivo: Evaluar el impacto del HSC y la autoinmunidad positiva en las complicaciones obstétricas y perinatales en nuestra población. Material y método: Estudio de cohortes retrospectivo en 435 mujeres con HSC (TSH entre 3,86 y 10μUI/ml, y FT4 normal) en el primer trimestre de la gestación, con seguimiento durante el embarazo. Se analizaron parámetros epidemiológicos y clínicos y se relacionaron con complicaciones obstétricas y perinatales en función de la presencia de autoinmunidad positiva (anticuerpos antiperoxidasa [aTPO] > 34 UI/ml). Resultados: La edad media fue de 31,3 años (desviación estándar: 5,2). El 17% de las pacientes presentaban aTPO positivos. La presencia de aTPO se asoció a antecedentes familiares de hipotiroidismo (p = 0,04), y con una mayor probabilidad de aborto (p = 0,009). En el análisis multivariante, los aTPO positivos suponían un aumento de probabilidad de presentar aborto de 10,25 veces. No se encontraron asociaciones estadísticamente significativas con el resto de las complicaciones obstétricas y perinatales. Conclusiones: En nuestro medio, las gestantes con HSC y autoinmunidad positiva presentan un mayor riesgo de aborto, pero no de otras complicaciones obstétricas y perinatales (AU)

Background: The impact of subclinical hypothyroidism (SH) and thyroid autoimmunity on obstetric and perinatal complications continues to be a matter of interest and highly controversial. Aim: To assess the impact of SH and autoimmunity in early pregnancy on the obstetric and perinatal complications in our population. Material and method: A retrospective cohort study in 435 women with SH (TSH ranging from 3.86 and 10 μIU/mL and normal FT4 values) in the first trimester of pregnancy. Epidemiological and clinical parameters were analyzed and were related to obstetric and perinatal complications based on the presence of autoimmunity (thyroid peroxidase antibodies [TPO] > 34 IU/mL). Results: Mean age was 31.3 years (SD 5.2). Seventeen percent of patients had positive TPO antibodies. Presence of positive autoimmunity was associated to a family history of hypothyroidism (P=.04) and a higher chance of miscarriage (P=.009). In the multivariate analysis, positive TPO antibodies were associated to a 10.25-fold higher risk of miscarriage. No statistically significant associations were found with all other obstetric and perinatal complications. Conclusions: In our region, pregnant women with SH and thyroid autoimmunity had a higher risk of miscarriage but not of other obstetric and perinatal complications (AU)

Impact of positive thyroid autoimmunity on pregnant women with subclinical hypothyroidism. / Impacto de la autoinmunidad antitiroidea positiva en gestantes con hipotiroidismo subclínico.

BACKGROUND: The impact of subclinical hypothyroidism (SH) and thyroid autoimmunity on obstetric and perinatal complications continues to be a matter of interest and highly controversial. AIM: To assess the impact of SH and autoimmunity in early pregnancy on the obstetric and perinatal complications in our population. MATERIAL AND METHOD: A retrospective cohort study in 435 women with SH (TSH ranging from 3.86 and 10 µIU/mL and normal FT4 values) in the first trimester of pregnancy. Epidemiological and clinical parameters were analyzed and were related to obstetric and perinatal complications based on the presence of autoimmunity (thyroid peroxidase antibodies [TPO] > 34 IU/mL). RESULTS: Mean age was 31.3 years (SD 5.2). Seventeen percent of patients had positive TPO antibodies. Presence of positive autoimmunity was associated to a family history of hypothyroidism (P=.04) and a higher chance of miscarriage (P=.009). In the multivariate analysis, positive TPO antibodies were associated to a 10.25-fold higher risk of miscarriage. No statistically significant associations were found with all other obstetric and perinatal complications. CONCLUSIONS: In our region, pregnant women with SH and thyroid autoimmunity had a higher risk of miscarriage but not of other obstetric and perinatal complications.

The Influence of Lipid and Proinflammatory Status on Maternal Uterine Blood Flow in Women With Late Onset Gestational Diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with increased proinflammatory cytokines and is also associated with adverse cardiovascular disease (CVD) outcomes later in life. We aim to evaluate the relationships between uterine arteries vascularization and endothelial dysfunction markers, proinflammatory cytokines, and glycemic and lipid profile in women with GDM. METHODS: Fifty pregnant women were recruited at the third trimester of pregnancy for a prospective cohort study. They were classified into 2 groups: control and GDM. Comparisons of maternal plasma concentrations of endothelial dysfunction markers (vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and plasminogen activator inhibitor 1), proinflammatory cytokines and mediators (interleukin 6 [IL-6], tumor necrosis factor α, vascular endothelial growth factor, placental growth factor, leptin, leukocyte count, and C-reactive protein), lipid profile, glucose, and glycosylated hemoglobin levels were performed. Mean uterine arteries Doppler pulsatility index (PI) was calculated and the relationships between the variables and PI were also analyzed. RESULTS: Women with GDM showed higher proinflammatory cytokines, however, endothelial dysfunction markers were similar in both groups. In the diabetic group, significant correlations were found between the mean uterine arteries PI and maternal IL-6 ( r = .56, P = .01), triglycerides ( r = .49; P = .03), total cholesterol/high-density lipoprotein cholesterol (HDL-c) ratio ( r = .61; P = .006), glucose (r = .62, P = .005), and glycosylated hemoglobin ( r = .48; P = .03). A negative significant correlation between mean uterine arteries PI and HDLc ( r = -.58; P = .02) was also found. CONCLUSION: The proinflammatory status, hyperlipidemia, and metabolic control correlate with uterine blood flow velocity waveforms in women with gestational diabetes.

Characterization of NO-Induced Nitrosative Status in Human Placenta from Pregnant Women with Gestational Diabetes Mellitus.

Dysregulation of NO production is implicated in pregnancy-related diseases, including gestational diabetes mellitus (GDM). The role of NO and its placental targets in GDM pregnancies has yet to be determined. S-Nitrosylation is the NO-derived posttranslational protein modification that can modulate biological functions by forming NO-derived complexes with longer half-life, termed S-nitrosothiol (SNO). Our aim was to examine the presence of endogenous S-nitrosylated proteins in cysteine residues in relation to antioxidant defense, apoptosis, and cellular signal transduction in placental tissue from control (n = 8) and GDM (n = 8) pregnancies. S-Nitrosylation was measured using the biotin-switch assay, while the expression and protein activity were assessed by immunoblotting and colorimetric methods, respectively. Results indicated that catalase and peroxiredoxin nitrosylation levels were greater in GDM placentas, and that was accompanied by reduced catalase activity. S-Nitrosylation of ERK1/2 and AKT was increased in GDM placentas, and their activities were inhibited. Activities of caspase-3 and caspase-9 were increased, with the latter also showing diminished nitrosylation levels. These findings suggest that S-nitrosylation is a little-known, but critical, mechanism by which NO directly modulates key placental proteins in women with GDM and, as a consequence, maternal and fetal anomalies during pregnancy can occur.

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)

¿Deberían modificarse los protocolos diagnóstico-terapéuticos de los incidentalomas suprarrenales? / Should the diagnostic and therapeutic protocols for adrenal incidentalomas be changed?

ANTECEDENTES: La prevalencia de los incidentalomas suprarrenales está aumentando por el envejecimiento de la población y el empleo de técnicas de imagen de alta resolución. Los protocolos actuales proponen un seguimiento de su estado funcional y morfológico exhaustivos, sin una evidencia clínica concluyente que lo avale MÉTODO: Estudio retrospectivo de 96 pacientes diagnosticados de incidentaloma adrenal entre 2008 y 2012. Se evalúan características clínicas, funcionales y de imagen, basales y durante el seguimiento. RESULTADOS: Inicialmente, 4 casos fueron intervenidos por hiperfunción (2 síndromes de Cushing y 2 feocromocitomas) y 5 por tamaño superior a 4 cm. Durante el seguimiento, tan solo se diagnosticó un caso de feocromocitoma y otro creció más de 1 cm, indicándose cirugía. En el 98,86% de los incidentalomas diagnosticados inicialmente como benignos y no funcionantes, no se objetivaron modificaciones funcionales y/o morfológicas en la evaluación final. CONCLUSIONES: Los resultados de nuestra serie cuestionan la validez de los protocolos de seguimiento de los incidentalomas adrenales vigentes en la actualidad, que deberían ser revaluados atendiendo a características de eficiencia mediante estudios prospectivos

BACKGROUND: The prevalence of adrenal incidentalomas is increasing with the aging of the population and the use of high resolution imaging technics. Current protocols propose a comprehensive monitoring of their functional and morphological state, but with no conclusive clinical evidence that endorses it. METHOD: Retrospective study of 96 patients diagnosed with adrenal incidentaloma between 2008 and 2012. We evaluated clinical, functional and imaging at baseline and during follow-up. RESULTS: Initially, 9 cases were surgically removed: 4 due to hyperfunction (2 Cushing syndromes and 2 pheochromocytomas) and 5 due to size larger than 4 cm. During follow-up one case of pheochromocytoma was diagnosed and another grew more than 1 cm, needing surgery. In 98.86% of nonfunctional and benign lesions, there was no functional and/or morphological changes in the final evaluation. CONCLUSIONS: The results of our study challenge the validity of current diagnostic-therapeutic protocols of incidentalomas, which should be reassessed in prospective studies taking into account efficiency characteristics