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Successful pregnancies rely on adaptations within the mother1, including marked changes within the immune system2. It has long been known that the thymus, the central lymphoid organ, changes markedly during pregnancy3. However, the molecular basis and importance of this process remain largely obscure. Here we show that the osteoclast differentiation receptor RANK4,5 couples female sex hormones to the rewiring of the thymus during pregnancy. Genetic deletion of Rank (also known as Tnfrsf11a) in thymic epithelial cells results in impaired thymic involution and blunted expansion of natural regulatory T (Treg) cells in pregnant female mice. Sex hormones, in particular progesterone, drive the development of thymic Treg cells through RANK in a manner that depends on AIRE+ medullary thymic epithelial cells. The depletion of Rank in the mouse thymic epithelium results in reduced accumulation of natural Treg cells in the placenta, and an increase in the number of miscarriages. Thymic deletion of Rank also results in impaired accumulation of Treg cells in visceral adipose tissue, and is associated with enlarged adipocyte size, tissue inflammation, enhanced maternal glucose intolerance, fetal macrosomia, and a long-lasting transgenerational alteration in glucose homeostasis, which are all key hallmarks of gestational diabetes. Transplantation of Treg cells rescued fetal loss, maternal glucose intolerance and fetal macrosomia. In human pregnancies, we found that gestational diabetes also correlates with a reduced number of Treg cells in the placenta. Our findings show that RANK promotes the hormone-mediated development of thymic Treg cells during pregnancy, and expand the functional role of maternal Treg cells to the development of gestational diabetes and the transgenerational metabolic rewiring of glucose homeostasis.
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Diabetes Gestacional/inmunología , Muerte Fetal/etiología , Receptor Activador del Factor Nuclear kappa-B/metabolismo , Linfocitos T Reguladores/inmunología , Timo/inmunología , Adipocitos/patología , Animales , Proliferación Celular , Diabetes Gestacional/etiología , Diabetes Gestacional/metabolismo , Diabetes Gestacional/patología , Células Epiteliales/inmunología , Femenino , Feto/inmunología , Feto/metabolismo , Feto/patología , Glucosa/metabolismo , Intolerancia a la Glucosa/genética , Humanos , Grasa Intraabdominal/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Placenta/inmunología , Placenta/patología , Embarazo , Receptor Activador del Factor Nuclear kappa-B/deficiencia , Receptor Activador del Factor Nuclear kappa-B/genética , Linfocitos T Reguladores/citología , Timo/citología , Factores de Transcripción/metabolismo , Proteína AIRERESUMEN
BACKGROUND: Tranexamic acid is an antifibrinolytic drug that is commonly administered for obstetric haemorrhage. Conventional viscoelastic tests are not sensitive to tranexamic acid, but the novel ClotPro® TPA-test can measure tranexamic acid-induced inhibition of fibrinolysis. We aimed to evaluate the TPA-test in pregnant and non-pregnant women. METHODS: We performed an in vitro study of whole blood samples spiked with tranexamic acid from pregnant women in the first, second, and third trimester (n=20 per group) and from non-pregnant women (n=20). We performed ClotPro TPA-tests of whole blood sample and ClotPro EX-tests, FIB-tests, and TPA-tests. RESULTS: Clot lysis was inhibited in a concentration-dependent manner up to a tranexamic acid concentration of 6.25 mg L-1. At tranexamic acid concentrations of 12.5 mg L-1 and above, clot lysis was completely inhibited. The concentration-effect relationship of tranexamic acid did not differ in a clinically important manner in blood from pregnant women across all three trimesters or from non-pregnant controls. A median maximum lysis cut-off value of at9 least 16% (25-75th percentiles 15-18), a median clot lysis time of 3600 s (25-75th percentiles 3600-3600), or both was associated with a tranexamic acid concentration of least 12.5 mg L-1. CONCLUSIONS: The ClotPro® TPA-test is sensitive in detecting inhibition of fibrinolysis by tranexamic acid in whole blood samples of pregnant and non-pregnant women. The concentration-effect relationship of tranexamic acid to inhibit fibrinolysis in whole blood did not differ for women in the first, second, and third trimester or for non-pregnant women.
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Antifibrinolíticos , Ácido Tranexámico , Femenino , Humanos , Embarazo , Fibrinólisis , Ácido Tranexámico/farmacología , Activador de Tejido Plasminógeno/farmacología , Tiempo de Lisis del Coágulo de Fibrina , Antifibrinolíticos/farmacologíaRESUMEN
The rs10830963 variant of the Melatonin Receptor 1B (MTNR1B) gene is associated with the development of gestational diabetes mellitus (GDM). We hypothesized that carrying the rs10830963/G risk allele had effect on antenatal insulin therapy (AIT) initiation in GDM in a body mass index (BMI)-dependent manner. Design: In this post hoc analysis the MTNR1B rs10830963 genotype and the clinical data of 211 Caucasian GDM patients were assessed. As a first step, a pre-pregnancy BMI threshold was determined where the effect of MTNR1B rs10830963/G allele carrying on AIT initiation was the most significant using logistic regression. Maternal age adjusted real-life odds ratios (OR) values were calculated. The chi-square test was also used to calculate the p value and 10.000 bootstrap simulations were performed in each case to re-assess the statistical power and the OR. Carrying the MTNR1B rs10830963/G allele increased the odds of AIT initiation (OR = 5.2, p = 0.02 [χ² test], statistical power = 0.53) in GDM patients with pre-pregnancy BMI ≥ 29 kg/m². The statistical power reached 0.77, when the pre-pregnancy BMI cutoff of 27 kg/m² was used and the genetic effect on AIT initiation was still significant, but only using the logistic regression model. Carrying the MTNR1B rs10830963/G risk allele-in interaction with pre-pregnancy BMI-is likely be considered as a candidate pharmacogenetic marker of antenatal insulin therapy initiation and should be further assessed in precision medicine trials in GDM.
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Alelos , Índice de Masa Corporal , Diabetes Gestacional/tratamiento farmacológico , Diabetes Gestacional/etiología , Variación Genética , Insulina/uso terapéutico , Receptor de Melatonina MT2/genética , Adulto , Biomarcadores , Glucemia , Diabetes Gestacional/metabolismo , Femenino , Humanos , Oportunidad Relativa , Farmacogenética , Embarazo , Resultado del TratamientoRESUMEN
AIMS/HYPOTHESIS: Accurate prevalence estimates for gestational diabetes mellitus (GDM) among pregnant women in Europe are lacking owing to the use of a multitude of diagnostic criteria and screening strategies in both high-risk women and the general pregnant population. Our aims were to report important risk factors for GDM development and calculate the prevalence of GDM in a cohort of women with BMI ≥29 kg/m2 across 11 centres in Europe using the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)/WHO 2013 diagnostic criteria. METHODS: Pregnant women (n = 1023, 86.3% European ethnicity) with a BMI ≥29.0 kg/m2 enrolled into the Vitamin D and Lifestyle Intervention for GDM Prevention (DALI) pilot, lifestyle and vitamin D studies of this pan-European multicentre trial, attended for an OGTT during pregnancy. Demographic, anthropometric and metabolic data were collected at enrolment and throughout pregnancy. GDM was diagnosed using IADPSG/WHO 2013 criteria. GDM treatment followed local policies. RESULTS: The number of women recruited per country ranged from 80 to 217, and the dropout rate was 7.1%. Overall, 39% of women developed GDM during pregnancy, with no significant differences in prevalence across countries. The prevalence of GDM was high (24%; 242/1023) in early pregnancy. Despite interventions used in the DALI study, a further 14% (94/672) had developed GDM when tested at mid gestation (24-28 weeks) and 13% (59/476) of the remaining cohort at late gestation (35-37 weeks). Demographics and lifestyle factors were similar at baseline between women with GDM and those who maintained normal glucose tolerance. Previous GDM (16.5% vs 7.9%, p = 0.002), congenital malformations (6.4% vs 3.3%, p = 0.045) and a baby with macrosomia (31.4% vs 17.9%, p = 0.001) were reported more frequently in those who developed GDM. Significant anthropometric and metabolic differences were already present in early pregnancy between women who developed GDM and those who did not. CONCLUSIONS/INTERPRETATION: The prevalence of GDM diagnosed by the IADPSG/WHO 2013 GDM criteria in European pregnant women with a BMI ≥29.0 kg/m2 is substantial, and poses a significant health burden to these pregnancies and to the future health of the mother and her offspring. Uniform criteria for GDM diagnosis, supported by robust evidence for the benefits of treatment, are urgently needed to guide modern GDM screening and treatment strategies.
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Diabetes Gestacional/epidemiología , Obesidad/epidemiología , Adulto , Comorbilidad , Europa (Continente)/epidemiología , Femenino , Humanos , Embarazo , Prevalencia , Adulto JovenRESUMEN
BACKGROUND: Tissue-specific dipeptidyl-peptidase 4 (DPP4) dysregulation has been described in adults with diabetes mellitus. The DPP4 -incretin system has not been studied in foetal life. In this study, DPP4 activity and glucagon-like peptide-1 (GLP-1) levels were assessed in cord blood of neonates born to women with gestational diabetes mellitus (GDM) and nondiabetic controls. MATERIAL AND METHODS: This study has been conducted in two Hungarian and one Austrian centres. PATIENTS: A total of 568 pregnant women were enrolled in the study after their OGTT between the 24th and 28th gestational week. Cord blood samplings with DPP4 activity and GLP-1 level measurements were possible in 270 (DPP4: 159 control, 111 GDM) and 112 (GLP-1: 72 control, 40 GDM) cases. OGTT (24-28th gestational week) and cord blood sampling at delivery were performed. Cord serum DPP4 activity was determined in a continuous monitoring microplate-based kinetic assay, and cord plasma GLP-1 was measured using a fluorescence ELISA method. RESULTS: Cord serum DPP4 activity was lower in GDM [mean (95% CI): 28.07 U/L (26.32-29.82 U/L)] than in controls [31.61 U/L (29.93-33.29 U/L), MWU P = 0.0015]. Cord plasma active GLP-1 levels were close to the lower detection limit and were not altered in GDM (control: mean = 3.43 pM, 95% CI: 3.04-3.82 pM, GDM: mean = 3.61 pM, 95% CI: 2.96-4.28 pM - MWU test P = 0.6). CONCLUSIONS: Decreased cord serum DPP4 activity in gestational diabetes mellitus might be the result of an adaptive foetal response or an early dysregulation in the entero-insular axis with consequences beyond the incretin system. Cord plasma GLP-1 levels may reflect the missing oral intake with a limited glucose sensing of L cells via the circulation in foetal life.
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Diabetes Gestacional/enzimología , Dipeptidil Peptidasa 4/metabolismo , Sangre Fetal/metabolismo , Adulto , Glucemia/metabolismo , Estudios de Casos y Controles , Diabetes Gestacional/dietoterapia , Diabetes Gestacional/tratamiento farmacológico , Femenino , Péptido 1 Similar al Glucagón/metabolismo , Humanos , Hipoglucemiantes/uso terapéutico , Insulinas/uso terapéutico , Embarazo , Resultado del EmbarazoRESUMEN
BACKGROUND: Medical staff's influence on patient outcomes has become a subject of interest. We evaluated experienced midwives and compared their performance concerning perineal lacerations (PL). METHODS: In a retrospective cohort study, 1937 women with singleton pregnancies who had delivered spontaneously with a cephalic presentation by experienced midwives in the Medical University of Vienna from January 2009 to April 2014 were included. As predictive parameters, we included basic patient-, pregnancy- and delivery-related characteristics including the individual midwife who delivered the child. The incidence of PL was the main outcome measure. RESULTS: Overall PL and severe PL were found in 508/1937 (26.2%) and 19/1937 women (1.0%), respectively. In a multivariate analysis for PL of any degree, maternal age (ß = 0.170 ± 0.080), gestational age at delivery (ß = 0.190 ± 0.320), and birth weight (ß = 0.002 ± 0.000) significantly increased the risk, whereas multiparity (ß = -0.379 ± 0.141) and mediolateral episiotomy (ß = -1.514 ± 0.284) decreased it (p < 0.05). In addition, the individual midwife who delivered the child was a significant influencing factor, with ß-values ranging from -0.028 to 0.899 compared to the reference midwife. For severe PL, the midwife was not of significant influence. CONCLUSIONS: The individual midwife is an independent factor that influences the risk for overall PL, not for severe PL. Other risk factors include maternal age, gestational age at delivery, birth weight, parity and episiotomy.
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Parto Obstétrico/efectos adversos , Laceraciones/epidemiología , Partería/estadística & datos numéricos , Complicaciones del Trabajo de Parto/epidemiología , Perineo/lesiones , Adulto , Austria/epidemiología , Competencia Clínica , Parto Obstétrico/métodos , Episiotomía/estadística & datos numéricos , Femenino , Edad Gestacional , Humanos , Incidencia , Laceraciones/etiología , Edad Materna , Complicaciones del Trabajo de Parto/etiología , Paridad , Embarazo , Estudios Retrospectivos , Factores de RiesgoRESUMEN
INTRODUCTION: Gremlin-1 is a peptide that functions as an antagonist to bone morphogenic proteins and is overexpressed in obesity and type 2 diabetes mellitus. Gremlin-1 has not yet been investigated in pregnancy, pregnancy-related insulin resistance or gestational diabetes mellitus (GDM). PATIENTS AND METHODS: Gremlin-1 levels were measured throughout the pregnancy of 58 women at high risk for GDM at the Medical University of Vienna. Furthermore, an oral glucose tolerance test, fasting insulin, fasting glucose, sex hormones, blood lipids, liver and renal parameters, and markers of bone development were evaluated at two points during pregnancy (< 20 weeks of gestation (GW), GW 24-28) and 12-14 weeks postpartum. RESULTS: Gremlin-1 levels decreased from < 20 GW (mean = 9.2 pg/ml, SD = 8.4 pg/ml) to GW 24-28 (mean = 6.7 pg/ml, SD = 5.7 pg/ml, p = 0.033) and increased again postpartum, albeit not significantly (mean = 10.7 pg/ml, SD = 13.1 pg/ml, p = 0.339). During pregnancy, Gremlin-1 levels correlated negatively with osteocalcin and procollagen type I aminoterminal propeptide (P1NP), markers of bone health. Concerning glucose metabolism, Gremlin-1 levels were inversely related to the Insulinogenic Index at GW < 20. However, Gremlin-1 levels were not significantly different between women with normal glucose tolerance and GDM during pregnancy. Postpartum, Gremlin-1 was associated with the fatty liver index, osteocalcin levels, diastolic blood pressure and weight. CONCLUSION: Gremlin-1 levels decreased significantly during pregnancy. The biomarker is not related to GDM status, but correlates negatively with the Insulinogenic Index, an index related to beta cell function. Trial Registry Number ACTRN12616000924459.
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Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Hígado Graso , Resistencia a la Insulina , Femenino , Humanos , Embarazo , Glucemia/metabolismo , Densidad Ósea , Glucosa , Insulina/metabolismo , Resistencia a la Insulina/fisiología , Osteocalcina , Periodo PospartoRESUMEN
(1) Background: Vaccination rates for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) are low in Austria. International obstetric societies recommend the SARS-CoV-2 mRNA vaccination for women in puerperium. (2) Methods: A prospective two-stage cohort study was conducted at the Medical University of Vienna between October 2022 and December 2022. Firstly, women in puerperium were assigned to the evaluation group (step 1), and secondly, another cohort of unvaccinated women were randomly assigned to study group A (written briefing) or B (written and oral briefing) (step 2). We evaluated the vaccination status among women in the evaluation group and the willingness to receive the vaccination in all three cohorts. (3) Results: We included 217 women in puerperium (evaluation: n = 69, A: n = 68; B: n = 80). In the evaluation group, 66.7% (n = 46/69) of the women were unvaccinated. A total of 45.7% (21/46) of the unvaccinated women categorically declined the SARS-CoV-2 vaccination. A total of 26.5% (n = 18/68) of women in study group A, and 43.8% (n = 35/80) of women in study group B expressed their willingness to receive the vaccination (p = 0.029). There were no differences in willingness to receive the vaccination between different age strata of women in study groups A and B. (D) Conclusion: Our qualitative data demonstrate a benefit from oral counseling in addition to written briefing in order to increase the willingness to receive the vaccination among women in puerperium.
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Vitamin D deficiency is a common finding in overweight/obese pregnant women and is associated with increased risk for adverse pregnancy outcome. Both maternal vitamin D deficiency and maternal obesity contribute to metabolic derangements in pregnancy. We aimed to assess the effects of vitamin D3 supplementation in pregnancy versus placebo on maternal and fetal lipids. Main inclusion criteria were: women <20 weeks' gestation, BMI ≥ 29 kg/m2. Eligible women (n = 154) were randomized to receive vitamin D3 (1600 IU/day) or placebo. Assessments were performed <20, 24−28 and 35−37 weeks and at birth. Linear regression models were used to assess effects of vitamin D on maternal and cord blood lipids. In the vitamin D group significantly higher total 25-OHD and 25-OHD3 levels were found in maternal and cord blood compared with placebo. Adjusted regression models did not reveal any differences in triglycerides, LDL-C, HDL-C, free fatty acids, ketone bodies or leptin between groups. Neonatal sum of skinfolds was comparable between the two groups, but correlated positively with cord blood 25-OH-D3 (r = 0.34, p = 0.012). Vitamin D supplementation in pregnancy increases maternal and cord blood vitamin D significantly resulting in high rates of vitamin D sufficiency. Maternal and cord blood lipid parameters were unaffected by Vitamin D3 supplementation.
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Diabetes Gestacional , Deficiencia de Vitamina D , Distribución de la Grasa Corporal , Colecalciferol/uso terapéutico , LDL-Colesterol , Diabetes Gestacional/prevención & control , Suplementos Dietéticos , Ácidos Grasos no Esterificados , Femenino , Humanos , Recién Nacido , Cuerpos Cetónicos , Leptina , Estilo de Vida , Obesidad , Sobrepeso , Embarazo , Resultado del Embarazo , Mujeres Embarazadas , Triglicéridos , Vitamina D , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/tratamiento farmacológico , VitaminasRESUMEN
The objective of the present study was to assess (i) the effects of immigration on the outcome of 200 consecutive singleton pregnancies in women with overt diabetes as well as (ii) gender-specific differences in cardiovascular risk factor profile and the achievement of therapeutic targets in type 2 diabetic subjects with migration background (n = 50). In pregnant subjects, baseline characteristics at admission, pregnancy outcome and the rate of obstetrical complications were similar in immigrant and non-immigrant women. Type 2 diabetes and also preconceptionally undiagnosed diabetes were significantly more frequent in women with migration background. Following delivery, immigrants presented with a worse metabolic profile, including higher triglyceride and nonHDL levels, than the indigenous population. Furthermore, within diabetic subjects with a migration background, non-pregnant women feature a more adverse cardiovascular risk factor profile than men. However, no gender-specific differences in the total adherence to clinical recommendations according to clinical recommendations have been found.
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Diabetes Mellitus Tipo 1/etnología , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 2/etnología , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Gestacional/etnología , Diabetes Gestacional/epidemiología , Emigrantes e Inmigrantes/estadística & datos numéricos , Resultado del Embarazo/etnología , Resultado del Embarazo/epidemiología , Embarazo en Diabéticas/etnología , Embarazo en Diabéticas/epidemiología , Adulto , Presión Sanguínea , Índice de Masa Corporal , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etnología , Estudios Transversales , Femenino , Alemania , Hemoglobina Glucada/análisis , Hospitales Universitarios , Humanos , Recién Nacido , Masculino , Cooperación del Paciente/etnología , Embarazo , Factores de RiesgoRESUMEN
Recent studies have shown higher levels of CTRP-1 (C1QTNF-related protein) in patients with type 2 diabetes compared to controls. We aimed at investigating CTRP-1 in gestational diabetes mellitus (GDM). CTRP-1 levels were investigated in 167 women (93 with normal glucose tolerance (NGT), 74 GDM) of a high-risk population for GDM. GDM was further divided into GDM subtypes depending on a predominant insulin sensitivity issue (GDM-IR) or secretion deficit (GDM-IS). Glucose tolerance was assessed with indices [Matsuda index, Stumvoll first phase index, insulin-secretion-sensitivity-index 2 (ISSI-2), area-under-the-curve (AUC) insulin, AUC glucose] derived from an oral glucose tolerance test (oGTT) performed at < 21 and 24-28 weeks of gestation. In pregnancy, CTRP-1 levels of GDM (76.86 ± 37.81 ng/ml) and NGT (82.2 ± 35.34 ng/ml; p = 0.104) were similar. However, GDM-IR women (65.18 ± 42.18 ng/ml) had significantly lower CTRP-1 levels compared to GDM-IS (85.10 ± 28.14 ng/ml; p = 0.009) and NGT (p = 0.006). CTRP-1 levels correlated negatively with weight, AUC insulin, Stumvoll first phase index, bioavailable estradiol and positively with HbA1c, Matsuda Index and ISSI-2. A multiple regression analysis revealed bioavailable estradiol (ß = - 0.280, p = 0.008) and HbA1c (ß = 0.238; p = 0.018) as the main variables associated with CTRP-1 in GDM. Postpartum, waist and hip measurements were predictive of CRTP-1 levels instead. CTRP-1 levels were higher postpartum than during pregnancy (91.92 ± 47.27 vs.82.44 ± 38.99 ng/ml; p = 0.013). CTRP-1 is related to insulin resistance in pregnancy and might be a metabolic biomarker for insulin resistance in GDM. CTRP-1 levels were significantly lower during pregnancy than postpartum, probably due to rising insulin resistance during pregnancy.
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Diabetes Gestacional/metabolismo , Resistencia a la Insulina , Proteínas/metabolismo , Adulto , Glucemia/metabolismo , Femenino , Intolerancia a la Glucosa , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/metabolismo , Periodo Posparto , EmbarazoRESUMEN
Secretagogin (SCGN) is a calcium binding protein related to insulin release in the pancreas. Although SCGN is not co-released with insulin, plasma concentrations have been found to be increased in type 2 diabetes mellitus patients. Until now, no study on SCGN levels in pregnancy or patients with gestational diabetes mellitus (GDM) has been published. In 93 women of a high-risk population for GDM at the Medical University of Vienna, secretagogin levels of 45 GDM patients were compared to 48 women with a normal glucose tolerance (NGT). Glucose tolerance, insulin resistance and secretion were assessed with oral glucose tolerance tests (OGTT) between the 10th and 28th week of gestation (GW) and postpartum. In all women, however, predominantly in women with NGT, there was a significant positive correlation between SCGN levels and Stumvoll first (rp = 0.220, p = 0.032) and second phase index (rp = 0.224, p = 0.028). SCGN levels were not significantly different in women with NGT and GDM. However, SCGN was higher postpartum than during pregnancy (postpartum: 88.07 ± 35.63 pg/mL; pregnancy: 75.24 ± 37.90 pg/mL, p = 0.004). SCGN was directly correlated with week of gestation (rp = 0.308; p = 0.021) and triglycerides (rp = 0.276; p = 0.038) in women with GDM. Therefore, SCGN is related to insulin secretion and hyperinsulinemia during pregnancy; however, it does not display differences between women with NGT and GDM.
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BACKGROUND & AIMS: Obesity is associated with lower breastfeeding rates. The underlying pathophysiological mechanisms are not well-understood, but there is increasing evidence on an association between parameters of maternal glucose metabolism and prolactin concentrations. In this cross-sectional observational study we investigate the relationship between breastfeeding, maternal obesity, and maternal glucose metabolism postpartum with beta cell function as a primary outcome measure. METHODS: We investigated 106 women (44% obese) prospectively recruited during the pregnancy, who underwent a 75 g - 2 h oral glucose tolerance test (OGTT) between the 3rd and 5th months postpartum. At this time point, we tested the relationship between breastfeeding status, maternal prolactin concentrations, maternal obesity, and fasting and dynamic indices of glucose metabolism using multivariate logistic regression in a post hoc analysis of prospective observational data. RESULTS: During the study visit at a mean of 122 (SE 9.3) days after delivery, 47% of obese women and 68% of non-obese women were breastfeeding (p < 0.05). Lactation and higher prolactin concentrations were associated with lower prepregnancy weight and lower postpartum insulin concentrations. Prehepatic beta-cell function was decreased in both obese (mean (SD); 0.16 (0.04) vs. 0.19 (0.05), p < 0.05) and non-obese (0.12 (0.05) vs. 0.16 (0.06), p < 0.01), lactating women. Obese lactating women have significantly lower first (1135.1 (306.7) pmol/L vs. 1517.3 (475.8) pmol/L, p < 0.01) and second phase insulin secretion (mean (SD), 300.2 (70.7) pmol/L vs. 393.1 (115.5) pmol/L, p < 0.01) as shown by Stumvoll indices when comparing to obese non-lactating women. Prehepatic beta-cell function and Stumvoll 1st phase insulin secretion index, but not BMI, were independently and negatively associated with breastfeeding and circulating prolactin concentrations. CONCLUSIONS: Beta-cell function during lactation relates to breastfeeding and circulating prolactin concentrations independently of obesity. The well-known positive effects of lactation on maternal and offspring outcomes might reflect a causative relationship of higher breastfeeding rates in metabolically healthier women.
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Lactancia Materna , Células Secretoras de Insulina/metabolismo , Obesidad/metabolismo , Adulto , Glucemia/análisis , Glucemia/metabolismo , Diabetes Gestacional/metabolismo , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/sangre , Insulina/metabolismo , Lactancia/metabolismo , Lactancia/fisiología , Embarazo , Prolactina/sangre , Prolactina/metabolismo , Estudios ProspectivosRESUMEN
Gestational diabetes mellitus (GDM) is defined as a glucose tolerance disorder with onset during pregnancy and is associated with increased feto-maternal morbidity as well as long-term complications in mother and child. Women who fulfil the criteria of a manifest diabetes in early pregnancy (fasting plasma glucose >126â¯mg/dl, spontaneous glucose level >200â¯mg/dl or HbA1câ¯> 6.5% before 20 weeks of gestation) should be classified as having manifest diabetes in pregnancy and treated as such. Screening for undiagnosed type 2 diabetes at the first prenatal visit (evidence level B) is particularly recommended in women at increased risk (history of GDM or prediabetes, malformation, stillbirth, successive abortions or birth weight >4500â¯g in previous pregnancies, obesity, metabolic syndrome, age >35 years, vascular disease, clinical symptoms of diabetes, e.â¯g. glucosuria, or ethnic groups with increased risk for GDM/T2DM, e.g. Arabian countries, south and southeast Asia and Latin America). A GDM is diagnosed by an oral glucose tolerance test (OGTT) or a fasting glucose concentration ≥92â¯mg/dl. Performance of the OGTT (120â¯min, 75â¯g glucose) may already be indicated in the first trimester in high risk women but is mandatory between 24-28 gestational weeks in all pregnant women with previous non-pathological glucose metabolism (evidence level B). Based on the results of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study and following the recent WHO recommendations, GDM is present if the fasting plasma glucose level exceeds 92â¯mg/dl, the 1â¯h level exceeds 180â¯mg/dl or the 2â¯h level exceeds 153â¯mg/dl after glucose loading (OGTT international consensus criteria). A single increased value is sufficient for the diagnosis and a strict metabolic control is mandatory. After bariatric surgery an OGTT is not recommended due to the risk of postprandial hypoglycemia. All women with GDM should receive nutritional counselling, be instructed in self-monitoring of blood glucose and to increase physical activity to moderate intensity levels, if not contraindicated. If blood glucose levels cannot be maintained in the therapeutic range (fasting <95â¯mg/dl and 1â¯h postprandial <140â¯mg/dl) insulin therapy should be initiated as first choice. Maternal and fetal monitoring is required in order to minimize maternal and fetal/neonatal morbidity and perinatal mortality. After delivery all women with GDM have to be re-evaluated by a 75â¯g OGTT (WHO criteria) 4-12 weeks postpartum to reclassify the glucose tolerance and every 2 years in cases of normal glucose tolerance (evidence level B). All women have to be informed about their (sevenfold increased relative) risk of developing type 2 diabetes (T2DM) at follow-up and possible preventive measures, in particular weight management, healthy diet and maintenance/increase of physical activity. Monitoring of the development of children and recommendations for a healthy lifestyle are necessary for the whole family. Regular obstetric examinations including ultrasound examinations are recommended. Within the framework of neonatal care, neonates of GDM mothers should undergo blood glucose measurements and if necessary appropriate measures should be initiated.
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Diabetes Gestacional , Resultado del Embarazo , Adulto , Glucemia/análisis , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/prevención & control , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/prevención & control , Etnicidad , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Recién Nacido , Insulina , Masculino , Guías de Práctica Clínica como Asunto , EmbarazoRESUMEN
OBJECTIVE: In our randomized controlled trial, we investigated the impact of healthy eating (HE) aiming for restricted gestational weight gain (GWG) and physical activity (PA) interventions on maternal and neonatal lipid metabolism. RESEARCH DESIGN AND METHODS: Obese pregnant women (n = 436) were included before 20 weeks' gestation and underwent glucose testing (oral glucose tolerance test) and lipid profiling at baseline and 24-28 and 35-37 gestational weeks after an at least 10-h overnight fast. This secondary analysis had a factorial design with comparison of HE (n = 221) versus no HE (n = 215) and PA (n = 218) versus no PA (n = 218). Maternal changes in triglycerides (TG), LDL cholesterol, HDL cholesterol, free fatty acids (FFAs), and leptin from baseline to end of pregnancy and neonatal outcomes were analyzed using general linear models with adjustment for relevant parameters. RESULTS: At 24-28 weeks' gestation, FFAs (mean ± SD, 0.60 ± 0.19 vs. 0.55 ± 0.17 mmol/L, P < 0.01) were increased after adjustment for FFA at baseline, maternal age, BMI at time of examination, gestational week, insulin resistance, self-reported food intake, self-reported physical activity, and maternal smoking, and GWG was lower (3.3 ± 2.6 vs. 4.3 ± 2.8 kg, P < 0.001, adjusted mean differences -1.0 [95% CI -1.5; -0.5]) in HE versus no HE. Fasting glucose levels (4.7 ± 0.4 vs. 4.6 ± 0.4 mmol/L, P < 0.05) and 3-ß-hydroxybutyrate (3BHB) (0.082 ± 0.065 vs. 0.068 ± 0.067 mmol/L, P < 0.05) were higher in HE. Significant negative associations between carbohydrate intake and FFA, 3BHB, and fasting glucose at 24-28 weeks' gestation were observed. No differences between groups were found in oral glucose tolerance test or leptin or TG levels at any time. Furthermore, in PA versus no PA, no similar changes were found. In cord blood, elevated FFA levels were found in HE after full adjustment (0.34 ± 0.22 vs. 0.29 ± 0.16 mmol/L, P = 0.01). CONCLUSIONS: HE intervention was associated with reduced GWG, higher FFAs, higher 3BHB, and higher fasting glucose at 24-28 weeks of gestation, suggesting induction of lipolysis. Increased FFA was negatively associated with carbohydrate intake and was also observed in cord blood. These findings support the hypothesis that maternal antenatal dietary restriction including carbohydrates is associated with increased FFA mobilization.
Asunto(s)
Dieta Saludable/métodos , Estilo de Vida , Obesidad/sangre , Complicaciones del Embarazo/sangre , Atención Prenatal/métodos , Ácido 3-Hidroxibutírico/sangre , Adulto , Glucemia/análisis , Carbohidratos , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Carbohidratos de la Dieta/farmacología , Europa (Continente) , Ejercicio Físico/fisiología , Análisis Factorial , Ácidos Grasos no Esterificados/sangre , Femenino , Ganancia de Peso Gestacional , Prueba de Tolerancia a la Glucosa , Humanos , Hidroxibutiratos , Resistencia a la Insulina , Leptina/sangre , Modelos Lineales , Obesidad/terapia , Embarazo , Complicaciones del Embarazo/terapia , Resultado del Tratamiento , Triglicéridos/sangre , Aumento de PesoRESUMEN
The prevalence of obesity is growing worldwide, and strategies to overcome this epidemic need to be developed urgently. Bariatric surgery is a very effective treatment option to reduce excess weight and often performed in women of reproductive age. Weight loss influences fertility positively and can resolve hormonal imbalance. So far, guidelines suggest conceiving after losing maximum weight and thus recommend conception at least 12-24 months after surgery. As limited data of these suggestions exist, further evidence is urgently needed as well for weight gain in pregnancy. Oral glucose tolerance tests for the diagnosis of gestational diabetes mellitus (GDM) should not be performed after bariatric procedures due to potential hypoglycaemic adverse events and high variability of glucose levels after glucose load. This challenges the utility of the usual diagnostic criteria for GDM in accurate prediction of complications. Furthermore, recommendations on essential nutrient supplementation in pregnancy and lactation in women after bariatric surgery are scarce. In addition, nutritional deficiencies or daily intake recommendations in pregnant women after bariatric surgery are not well investigated. This review summarizes current evidence, proposes clinical recommendations in pregnant women after bariatric surgery, and highlights areas of lack of evidence and the resulting urgent need for more clinical investigations.
Asunto(s)
Cirugía Bariátrica , Obstetricia/normas , Embarazo , Salud de la Mujer/normas , Lactancia Materna , Diabetes Gestacional/diagnóstico , Femenino , Fertilidad , Humanos , Necesidades Nutricionales , Obesidad/epidemiología , Pérdida de PesoRESUMEN
A team of experts from the fields of gynaecology and obstetrics, diabetology, internal medicine, paediatrics and midwifery from Germany, Austria and Switzerland produced a new version of the existing S3 guideline on gestational diabetes. It replaces the recommendations of the German Association for Gynaecology and Obstetrics and the German Diabetes Association on the diagnosis and treatment of gestational diabetes from 2011 and is valid for the three German-speaking countries. The primary aim of the guideline is to improve and standardise the prevention, screening, diagnosis, treatment and follow-up of gestational diabetes through evidence-based recommendations for the outpatient and inpatient area. A large number of new studies and data published in the last few years required a comprehensive revision of the 2011 guideline. The new aspects include early screening of pregnant women with a high risk for diabetes or gestational diabetes, the validity of two-stage screening in the third trimester by means of the 50-g challenge test, as specified in the maternity guidelines, use of metformin instead of or in addition to insulin in gestational diabetes, and birth planning with GDM and/or macrosomia. The recommendations are based on the evidence from the literature, which was selected through a systematic external literature search. All recommendations had to pass through a consensus process. The present text corresponds to the practice guideline on gestational diabetes, which is an action-oriented short version of the evidence-based S3 guideline that can be viewed on the internet.
RESUMEN
OBJECTIVE: Risk factors are widely used to identify women at risk for gestational diabetes mellitus (GDM) without clear distinction by pregnancy period or oral glucose tolerance test (OGTT) time points. We aimed to assess the clinical risk factors for Hyperglycemia in pregnancy (HiP) differentiating by these two aspects. DESIGN AND METHODS: Nine hundred seventy-one overweight/obese pregnant women, enrolled in the DALI study for preventing GDM. OGTTs were performed at ≤19 + 6, 24-28 and 35-37 weeks (IADPSG/WHO2013 criteria). Women with GDM or overt diabetes at one time point did not proceed to further OGTTs. Potential independent variables included baseline maternal and current pregnancy characteristics. STATISTICAL ANALYSIS: Multivariate logistic regression. RESULTS: Clinical characteristics independently associated with GDM/overt diabetes were at ≤19 + 6 weeks, previous abnormal glucose tolerance (odds ratio (OR): 3.11; 95% CI: 1.41-6.85), previous GDM (OR: 2.22; 95% CI: 1.20-4.11), neck circumference (NC) (OR: 1.58; 95% CI: 1.06-2.36 for the upper tertile), resting heart rate (RHR, OR: 1.99; 95% CI: 1.31-3.00 for the upper tertile) and recruitment site; at 24-28 weeks, previous stillbirth (OR: 2.92; 95% CI: 1.18-7.22), RHR (OR: 3.32; 95% CI: 1.70-6.49 for the upper tertile) and recruitment site; at 35-37 weeks, maternal height (OR: 0.41; 95% CI: 0.20-0.87 for upper tertile). Clinical characteristics independently associated with GDM/overt diabetes differed by OGTT time point (e.g. at ≤19 + 6 weeks, NC was associated with abnormal fasting but not postchallenge glucose). CONCLUSION: In this population, most clinical characteristics associated with GDM/overt diabetes were non-modifiable and differed by pregnancy period and OGTT time point. The identified risk factors can help define the target population for future intervention trials.
Asunto(s)
Diabetes Gestacional/epidemiología , Edad Gestacional , Intolerancia a la Glucosa/epidemiología , Hiperglucemia/epidemiología , Obesidad/epidemiología , Complicaciones del Embarazo/epidemiología , Adulto , Glucemia/metabolismo , Estatura , Tamaño Corporal , Diabetes Gestacional/prevención & control , Dieta Saludable , Ejercicio Físico , Ayuno , Femenino , Prueba de Tolerancia a la Glucosa , Frecuencia Cardíaca , Humanos , Entrevista Motivacional , Cuello , Oportunidad Relativa , Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Mortinato/epidemiologíaRESUMEN
OBJECTIVE: Previous studies concluded that symptomatic prepubertal children with Gardnerella vaginalis infection should be investigated for child sexual abuse. Gardnerella vaginalis is only one out of a group of organism that cause bacterial vaginosis. The aim of the study was to report the frequency of bacterial colonization as well as sexually transmitted diseases and to correlate these data with patient characteristics. METHODS: Data were collected from 1996 to 2006. Medical records of 180 girls, median age at first sexual abuse 7.44 years (range 1-16, SD 3.937), have been evaluated retrospectively. SPSS software 12.0 has been used for statistical analysis. RESULTS: Only 18.3% of patients complained of vaginal discharge or pruritus. Sexually transmitted diseases were documented: Gonorrhoea 1 (1.8%, 56 tested), Chlamydia trachomatis 1 (1.6%, 62 tested), Syphilis 0 (0%, 5 tested), Trichomonas vaginalis 1 (0.7%, 136 tested) and HIV 0 (0%, 27 tested). Bacterial colonization were documented (121 tested): Gardnerella vaginalis 29 (24%), Enterobacteriaceae 50 (41.3%), Haemophilus influenzae 11 (9.1%), Streptococcus a haemolyticus 35 (28.9%), Streptococcus Group B 8 (6.6%), Staphylococcus Koag neg. 37 (30.6%), Staphylococcus aureus 10 (8.3%), Pseudomonas aeruginosa 4 (4.1%), Bacteroides 19 (15.7%), Prevotella 24 (19.8%), Klebsiella 4 (3.3%), Corynebacteria 20 (16.5%) and Ureaplasma 9 (7.4%). CONCLUSIONS: Sexually transmitted diseases are infrequent in children suspected for child sexual abuse. Bacterial colonization is common, however, not correlated with clinical symptoms (except for Bacteroides) and hymenal/vaginal injuries.