The Master's thesis entitled "Gestational Diabetes Diet" deals with the issue of eating habits and a lifestyle of women diagnosed with gestational diabetes mellitus during pregnancy. The theoretical part of the thesis describes the definition, causes and a mechanism of origin, consequences for mother and fetus and also deals with the diagnostic procedures and all possibilities of treatment of this disease. In this part, the diagnostic method analyzed by using the oGTT stress test and a diabetic diet - that together with other preventive measures (mainly physical aktivity) is the first choice in the treatment of pregnancy diabetes - are described in more details. The practical part of this master's thesis contains the results of a questionnaire survey in two groups of pregnant women - with already diagnosed gestational diabetes and before its diagnosis in the oGTT test. It also contains the results of the analysis of women with GDM diets. The analysis were processed by the NutriPro Expert diet program and the results are then compared with the current nutritional recommendations of the Czech Republic for pregnant and nursing women. The aim of this work was to map the eating habits and lifestyle of women with gestational diabetes and find out whether they meet current nutritional recommendations or...

O estudo das funções extra-esqueléticas da vitamina D vem ampliando-se nos últimos anos. Na gestação, a preocupação com os níveis de vitamina D maternos ocorre pela necessidade desta vitamina para a formação do esqueleto fetal e pela associação da hipovitaminose D com desfechos adversos materno-fetais. Para o recém-nascido (RN), as complicações incluem o baixo peso ao nascer, o comprometimento do crescimento longitudinal e as infecções respiratórias. Para a gestante, a deficiência de vitamina D vem sendo associada à alteração na homeostase glicêmica e ao aumento da incidência de diabetes gestacional (DG) , à pré-eclâmpsia e à vaginose bacteriana. Entretanto, a evidência científica atual ainda é controversa e não há definição estabelecida sobre o real benefício da suplementação da vitamina D na gestação. O diabetes gestacional, por sua vez, também está associado a desfechos adversos para a gestante e para a prole. Para o feto, há aumento da incidência de prematuridade, macrossomia, distócia de ombro e hipoglicemia neonatal; enquanto para a mãe, há associação com aumento da taxa de cesariana, pré-eclâmpsia e diabetes pós-gestacional. Desta forma, os desfechos adversos da hipovitaminose D e do DG presentes de forma simultânea na gestação podem ser aditivos. Este artigo propõe-se à revisão das repercussões da deficiência da vitamina D e do DG na gestação, para a mãe e para o RN, e discute a potencial repercussão da associação de ambas situações já que a hipovitaminose D pode estar relacionada com aumento da ocorrência de DG. / Extra-skeletal functions of vitamin D have been studied in the last years. During pregnancy, the concern with vitamin D levels is justified by its importance for the fetal skeleton development and by the association of hypovitaminosis D with adverse maternal and fetal outcomes. For the newborn, adverse outcomes include low birth weight, impaired longitudinal growth and respiratory infections. For the women, vitamin D deficiency has been associated with glucose homeostasis impairment and increased incidence of gestational diabetes (GD), preeclampsia and bacterial vaginosis. However, the available scientific data is still controversial and the real benefit of vitamin D supplementation during pregnancy is not defined. Hyperglycemia during pregnancy is also associated with increased rates of perinatal adverse outcomes. For the fetus and the newborn, GD is associated with an increased incidence of prematurity, macrosomia, shoulder dystocia and neonatal hypoglycemia; for the mother, there are increased rates of cesarean delivery, preeclampsia and type 2 diabetes. Therefore, adverse outcomes of hypovitaminosis D and GD present simultaneously during pregnancy could be additive. This manuscript aims to review the impact of vitamin D deficiency and of GD for the women and the newborn, and to discuss the potential association between these two clinical situations since hypovitaminosis D may increase the risk for GD.

The objective of this research was analyze the application of the public policies guidelines to the pregnant and postpartum with Gentional Diabetes Millitus during prenatal care, approaching the prevention, diagnosis and treatment. For this purpose, it was used a sample of 28 women with GDM at public and reference disease institute. An exploratory, descriptive and documentary survey was conducted approaching the quantitative. The instrument was a form and the technique, the structured interview. The data collection occurred from November 2012 to January 2013. First of all, we conducted a collection in charts and in antenatal card of the survey participants. Later on, the pregnates and postpartum women with Gestational Diabetes Mellitus diagnosed passed through an interview. The result of the research showed the balance between countries on public policies to pregnant and postpartum women with GDM, Brazil has the highest number of actions directed to gestational diabetes, for instance: prenatal care access in the first trimester of pregnancy; number of consultations according to those recommended by public policies, about the interval among childbirths, the majority took four years to get pregnant again, in the blood pressure check part, the pregnant women adhered during antenatal consultations over six times and the orientations received after the gestational diabetes diagnosis, the diet was the first guidance received. Nevertheless, remains the convenience of expansion and the creation of new public policies on health, targeted to pregnant and postpartum women with gestational diabetes mellitus, since this disease is still based on the guidelines established for chronic diseases. The DMG grows rapidly in uncomfortable level, and actions are insufficient to meet the health needs of this group. / A pesquisa teve como objetivo analisar a aplicaÃÃo das diretrizes das polÃticas pÃblicas dirigidas Ãs gestantes e puÃrperas portadoras de Diabetes Mellitus Gestacional, durante o prà natal, abordando a prevenÃÃo, o diagnÃstico e o tratamento. Para tanto, utilizou-se uma amostra com 28 mulheres portadoras de DMG em instituiÃÃo pÃblica e de referÃncia para a doenÃa. Realizou-se uma pesquisa documental, exploratÃria e descritiva com abordagem quantitativa. O instrumento foi um formulÃrio, e a tÃcnica, a entrevista estruturada. A coleta de dados ocorreu no perÃodo de novembro de 2012 a janeiro de 2013. Primeiramente foi realizada uma coleta em prontuÃrios e no cartÃo de prÃ-natal das participantes do estudo. No segundo momento foi aplicada uma entrevista Ãs gestantes e puÃrperas, com diagnÃstico de Diabetes Mellitus Gestacional. A pesquisa mostrou na comparaÃÃo entre paÃses sobre as polÃticas pÃblicas dirigidas Ãs gestantes e puÃrperas com DMG, o Brasil destacou-se com o maior nÃmero de aÃÃes direcionado para o diabetes gestacional, e, mediante o resultado da pesquisa tivemos os seguintes resultados: acesso ao prÃ-natal no primeiro trimestre da gestaÃÃo; nÃmero de consultas condizente com as preconizadas pelas polÃticas pÃblicas; em referÃncia ao intervalo entre partos a maioria levou mais de quatro anos para engravidar novamente; na categoria verificaÃÃo da pressÃo arterial, as gestantes aferiram-na durante as consultas de prÃ-natais mais de seis vezes e quanto Ãs orientaÃÃes recebidas apÃs a definiÃÃo do diagnÃstico de diabetes gestacional, a dieta foi a primeira orientaÃÃo recebida. Mesmo assim, pontua-se a conveniÃncia de ampliaÃÃo e a criaÃÃo de novas polÃticas pÃblicas na saÃde, direcionadas Ãs gestantes e puÃrperas portadoras de diabetes mellitus gestacional, uma vez que, essa patologia ainda se baseia nas normas e diretrizes estabelecidas para as doenÃas crÃnicas. O DMG cresce rapidamente em patamar pouco confortÃvel, e as aÃÃes sÃo insuficientes para suprir as necessidades de saÃde desse grupo.

O metoprolol, um fármaco aceito no tratamento da hipertensão durante a gestação, está disponível na clínica como mistura racêmica dos enantiômeros S-(-) e R-(+), embora o S-(-)-metoprolol seja considerado o eutômero em termos do bloqueio do receptor 1 adrenérgico. O presente estudo avalia a influência do Diabetes mellitus gestacional na disposição cinética e no metabolismo enantiosseletivos do metoprolol em parturientes hipertensas. As parturientes hipertensas investigadas (n=35) com idade gestacional de 35-42 semanas e fenotipadas como metabolizadoras extensivas tipo metoprolol, foram distribuídas nos grupos controle (n=24) ou portadoras de Diabetes mellitus gestacional (n=11). As parturientes foram tratadas com dose única oral de 100 mg de tartarato de metoprolol racêmico 1-11 h antes do parto. Foram coletadas amostras seriadas de sangue materno (0-24h) e no momento do parto foram coletados simultaneamente sangue materno, sangue do cordão umbilical e líquido amniótico. Os enantiômeros do metoprolol e seus metabólitos foram quantificados por LC-MS/MS ou por detecção por fluorescência. A disposição cinética do metoprolol é enantiosseletiva em parturientes hipertensas com observação de maiores concentrações plasmáticas (AUC0- 113,42 vs 62,65 ng.h/mL) e menor clearance total aparente (344,21 vs 623,14 L/h) para o eutômero S-(-)-metoprolol. A formação do metabólito -hidroximetoprolol também é estereosseletiva com favorecimento do novo centro quiral 1R (AUC0- 1R/1S=2,84). O favorecimento da formação do R-(+)-ácido O-desmetilmetoprolóico (AUC0- 2,77 vs 2,66 g.h/mL) explica o acúmulo plasmático do S-(-)-metoprolol. O Diabetes mellitus gestacional compensado prolonga o tmax para ambos os enantiômeros do metoprolol (1,5 vs 2,5 h) e ácido O-desmetilmetoprolóico (2,0 vs 3,5 h) e para todos os isômeros do -hidroximetoprolol (2,0 vs 3,0 h). O Diabetes mellitus gestacional compensado não altera as razões isoméricas de concentrações plasmáticas do metoprolol, -hidroximetoprolol e ácido O-desmetilmetoprolóico. As razões de concentrações líquido amniótico/plasma materno obtidas para ambos os enantiômeros do metoprolol (3,0 para o R-(+)-metoprolol e 3,2 para o S-(-)-metoprolol) e para os isômeros do -hidroximetoprolol (5,1 para o 1\'S,2R; 4,0 para o 1\'S,2S; 1,6 para o 1\'R,2R e 2,3 para o 1\'R,2S) evidenciam maiores concentrações dos fármacos no líquido amniótico do que no plasma materno. No entanto, os enantiômeros do ácido O-desmetilmetoprolóico atingem menores concentrações no líquido amniótico do que no plasma materno das parturientes hipertensas (líquido amniótico/plasma materno = 0,29 e 0,37 respectivamente para os enantiômeros R-(+)- e S-(-)). A distribuição transplacentária é próxima a 1 para ambos os enantiômeros do metoprolol e para todos os isômeros do -hidroximetoprolol e próxima a 0,8 para ambos os enantiômeros do ácido O-desmetilmetoprolóico em parturientes hipertensas. O Diabetes mellitus gestacional compensado reduz em aproximadamente 20% a distribuição transplacentária dos isômeros 1S,2S; 1R,2R; e 1R,2S--hidroximetoprolol mas não altera a distribuição dos enantiômeros do metoprolol. / Metoprolol is a drug accepted in the treatment of hypertension during pregnancy and it is clinically available as a racemic mixture of its enantiomers S-(-) and R-(+) metoprolol, although S-(-)-metoprolol is considered the eutomer responsible for 1 adrenergic receptor blockade.This study evaluates the influence of gestational Diabetes mellitus on the kinetic disposition and metabolism of metoprolol enantiomers in hypertensive parturients. The investigated parturients (n=35) presented gestational age within 35 to 42 weeks, were phenotyped as extensive metabolizers of metoprolol and were distributed in the control group (n=24) or in the gestational Diabetes mellitus group (n =11). The parturients were treated with single oral dose of 100 mg racemic metoprolol tartrate 1-11 h before delivery. Maternal blood samples were collected until 24h after drug administration, whereas maternal blood, umbilical cord blood and amniotic fluid were simultaneously collected at delivery. Metoprolol enantiomers and its metabolites were quantified by LC-MS/MS or by fluorescence detection. Kinetic disposition of metoprolol is enantioselective in hypertensive parturients with observation of higher plasma concentrations (AUC0- 113.42 vs 62.65 ng.h/mL) and lower apparent total clearance (344.21 vs 623.14 L/h) for the S-(-)-metoprolol eutomer. The formation of -hydroxymetoprolol metabolite is also stereoselective in favor of the new chiral center 1\'R (AUC0- 1\'R/1\'S = 2.84). The formation in favor of R-(+)-metoprolol acid metabolite (AUC0- 2.77 vs 2.66 g.h/mL) explains the plasma accumulation of S-(-)-metoprolol. Gestational Diabetes mellitus prolongs tmax for both metoprolol enantiomers (1.5 vs 2.5 h), metoprolol acid metabolite (2.0 vs 3.5 h) and for all -hydroxymetoprolol isomers (2.0 vs 3.0 h). Gestational Diabetes mellitus does not alter the isomeric ratios of plasma concentrations of metoprolol, -hydroxymetoprolol and metoprolol acid metabolite. The concentrations of both metoprolol enantiomers (amniotic fluid/maternal plasma = 3.0 for R-(+)-metoprolol and 3.2 for the S-(-)-metoprolol) and -hydroxymetoprolol isomers (liquid amniotic fluid/maternal plasma = 5.1 for 1\'S,2R; 4.0 for 1\'S,2S; 1.6 for 1\'R,2R and 2.3 for 1\'R,2S) are higher in amniotic fluid than in maternal plasma. However, metoprolol acid metabolite enantiomers reach lower concentrations in amniotic fluid than in maternal plasma of hypertensive parturients (amniotic fluid/maternal plasma = 0.29 and 0.37 respectively for the R-(+)- and S-(-)- enantiomers). The transplacental distribution is approximately 1 for both enantiomers of metoprolol and all isomers of -hydroxymetoprolol and approximately 0.8 for both metoprolol acid metabolite enantiomers in hypertensive parturients. Gestational Diabetes mellitus reduces in approximately 20% the transplacental distribution of the isomers 1\'S,2S; 1\'R,2R and 1\'R,2S--hidroximetoprolol but does not alter the transplacental distribution of both metoprolol enantiomers.

O labetalol, um anti-hipertensivo considerado seguro para uso em gestantes, está disponível na clínica como mistura de dois racematos (quatro estereoisômeros), sendo o isômero (R,R) antagonista e o (S,R) responsável pela atividade bloqueadora. O estudo investiga a influência do diabetes mellitus gestacional (DMG) na disposição cinética e no metabolismo estereosseletivos do labetalol administrado por via endovenosa ou oral. Foram investigadas 30 gestantes hipertensas distribuídas em 04 grupos: não diabéticas tratadas com dose única de 40 mg de cloridrato de labetalol endovenoso (grupo EVH, n=8) ou 100 mg de cloridrato de labetalol via oral (grupo VOH, n=9) e diabéticas tratadas com 40 mg de cloridrato de labetalol endovenoso (grupo EVD, n=6) ou 100 mg de cloridrato de labetalol via oral (grupo VOD, n=7). As amostras seriadas de sangue foram coletadas até 12 h (via oral) ou 15 h (via endovenosa) após a administração do cloridrato de labetalol. Os estereoisômeros do labetalol em plasma foram analisados em coluna de fase quiral Chirobiotic V empregando LC-MS-MS. Os parâmetros farmacocinéticos do labetalol inalterado e labetalol glicuronídeo foram calculados com auxílio do programa WinNonlin e avaliados empregando os testes de Mann-Whitney e Friedman com pós-teste de Dunn (p<0,05). A farmacocinética do labetalol não é estereosseletiva em gestantes diabéticas e não diabéticas tratadas com o fármaco por via endovenosa. No entanto, a administração oral de labetalol resulta em menores valores de área sob a curva concentração plasmática versus tempo (AUC) para o isômero ativo (R,R)-labetalol tanto em gestantes diabéticas (60,9 vs 162,7 vs 157,9 vs 114,6 ng.h/mL, respectivamente para (R,R,); (SR); (S,S,) e (R,S)) quanto não diabéticas (45,6 vs 84,2 vs 89,4 vs 78,3 ng.h/mL, respectivamente para (R,R,); (SR); (S,S,) e (R,S)). O DMG resulta em alterações na disposição cinética dos estereoisômeros do labetalol na administração oral. Os valores de AUC do isômero inativo (S,S)-labetalol (157,9 vs 89,4 ng.h/mL) e para o isômero -bloqueador (S,R)-labetalol (162.7 vs 84.2 ng.h/mL) são maiores (p<0,05) nas gestantes diabéticas do que nas gestantes não diabéticas. As gestantes diabéticas também mostram maior biodisponibilidade oral do isômero (S,R)-labetalol (54,7 vs 24,0 %) explicada pela reduzida eliminação pré-sistêmica conseqüente da menor capacidade de conjugação com o ácido glicurônico (68,4 vs 77,9 %). Os valores de AUC do isômero (S,R) aproximadamente 100 % maiores nas gestantess diabéticas tratadas com o fármaco por via oral (162,7 vs 84,2 ng.h/mL) pode ter relevância clínica considerando a atividade -bloqueadora do referido isômero. / Labetalol, a hypertensive agent considered to be safe for use by pregnant women, is clinically available as a mixture of two racemates, with the (R,R) isomer being a antagonist and the (S,R) isomer being responsible for the blocking activity. The study investigated the influence of gestational diabetes mellitus (GDM) on the kinetic disposition and stereoselective metabolism of labetalol administered by the intravenous or oral route. Thirty hypertensive pregnant women were divided into 4 groups: non-diabetic women treated with a single 40 mg dose of intravenous labetalol hydrochloride (IVH group, n=8) or with 100 mg labetalol hydrochloride by the oral route (OH group, n=9) and diabetic women treated with 40 mg intravenous labetalol hydrochloride (IVD), n=6) or with 100 mg labetalol hydrochloride by the oral route (OD, n=7). Serial blood samples were collected up to 12 h (oral route) or 15 h (intravenous route) after the administration of labetalol hydrochloride. The labetalol stereoisomers in plasma were analyzed with a chiral phase Chirobiotic V column by LC-MS-MS. The pharmacokinetic parameters of unchanged labetalol and glucuronide labetalol were calculated using the WinNolin software and analyzed by the Mann-Whitney and Friedman tests followed by the Dunn test (p<0.05). The pharmacokinetics of labetalol was not stereoselective in diabetic or non-diabetic pregnant women treated with the drug by the intravenous route. However, oral administration of labetalol resulted in lower values of the area under the plasma concentration versus time curve (AUC) for the active isomer (R,R)-labetalol both in diabetic (60.9 vs 162.7 vs 157.9 vs 114.6 ng.h/mL, respectively for (R,R,), (SR), (S,S,) and (R,S)) and non-diabetic pregnant women (45.6 vs 84.2 vs 89.4 vs 78.3 ng.h/mL, respectively for (R,R,), (SR), (S,S,) and (R,S)). GDM involves changes in the kinetic disposition of the stereoisomers of labetalol when administered by the oral route. The AUC values for the inactive (S,S)-labetalol (157.9 vs 89.4 ng.h/mL) and for the -blocking (S,R) isomer (162.7 vs 84.2 ng.h/mL) were higher (p<0.05) for the diabetic than the non-diabetic pregnant women. The diabetic pregnant women showed greater oral bioavailability of the (S,R)-labetalol isomer (54.7 vs 24.0 %), explained by the reduced pre-systemic elimination due to the lower capacity for conjugation with glucuronic acid (68.4 vs 77.9 %). The approximately 100 % higher AUC values of the (S,R) isomer for the diabetic pregnant women treated with the drug by the oral route may be of clinical relevance in view of the -blocking activity of the isomer in question.

Objetivo: Determinar potenciales factores de riesgo para diabetes mellitus gestacional (DMG). Métodos: Estudio de casos y controles realizado en el Hospital Alberto Sabogal mediante recolección de historias clínicas del 2009 a 2014. Se define como caso las gestantes con diagnóstico de DMG mediante una prueba de tolerancia oral a la glucosa (PTOG), previa glucosa en ayunas anormal y control a la gestante sin valores indicativos de DMG. Las variables de interés fueron paridad, antecedente de cesáreas, abortos y recién nacido con mayor peso. Modelos de regresión logística fueron calculados para estimar odd ratios (OR) e intervalos de confianza al 95% (IC95%). Resultados: Se incluyeron 84 casos y 336 controles. En el modelo multivariado, la multiparidad incrementó el riesgo de DMG (OR= 3,54; IC95% 1,55 – 8,14). También, antecedente de abortos, a partir del segundo aborto (OR= 3,40, IC95% 1,55 – 7,44) y cesáreas previas (1 cesárea OR= 3,5 IC95% 1,89 – 6,47 y 2+ cesáreas OR=8,35 IC95% 3,50 – 19,95). La multiparidad, dos o más abortos y mayor número de cesáreas son factores de riesgo para DMG. / Objectives: To identify risk factors for gestational diabetes mellitus (GDM). Methods: A case-control study was performed in Alberto Sabogal Hospital, collecting medical records from 2009 to 2014. A case was defined as a pregnant women diagnosed with GDM by an oral glucose tolerance test (OGTT) after an abnormal fasting glucose and control was defined as a pregnant women without GDM indicative values. The study outcome was GDM. The variables of interest were multiparity, previous cesarean section, abortions, newborn with the greatest weight. Logistic regression were used to calculate the odds ratio (OR) and a confidence interval of 95% (IC95%). Results: 84 cases and 336 controls were included. In the multivariate model, multiparity increased risk of GDM (OR= 3.54, 95% CI 1.55 to 8.14). As well history of abortions, from the second abortion (OR= 3.40, 95% CI 1.55 to 7.44) and previous cesarean section are also related (cesarean section 1 OR= 3.5 95% CI 1.89 to 6.47 and 2+ cesarean OR= 8.35 95% CI 3.50 to 19.95). Multiparity, two or more abortions, a biggest number of cesarean sections are GDM risk factors.

Introdução: Devido à fatores hormonais e mecânicos, a gestação e o parto provocam alterações que podem gerar disfunções do assoalho pélvico (DAP). Os estudos sobre as DAP no puerpério a curto prazo são escassos e fazem uso assistemático de métodos avaliativos. Objetivo: Identificar e avaliar as DAP no pós-parto imediato, um mês e três meses após o parto, comparando parto vaginal (PV), cesárea eletiva (CE) e cesárea intraparto (CI). Métodos: Estudo observacional longitudinal que avaliou mulheres até 48 horas (fase 1); um mês (fase 2) e três meses após o parto (fase 3). Utilizou-se o International Consultation on Incontinence Questionnaire (ICIQ-SF); o Índice de Incontinência Anal (IA) de Jorge-Wexner; a Escala Análoga Visual (EVA) para dor pélvica; o Pelvic Organ Prolapse Quantification system (POP-Q) e a perineometria dos Músculos do Assoalho Pélvico (MAP), além de questionário estruturado. Resultados: Foram avaliadas 227 pacientes na fase 1 (141 realizaram PV; 28 realizaram CI e 58 realizaram CE); 79 na fase 2 e 41 na fase 3. O escore do ICIQ-SF, índice de IA, EVA e perineometria não apresentaram diferenças significativas em relação ao tipo de parto. O ponto distal do colo uterino apresentou-se mais prolapsado no grupo PV. Conclusão: O tipo de parto não foi um fator significante para o desenvolvimento das DAP no pós-parto a curto prazo. Foi identificado que ocorreu recuperação fisiológica na funcionalidade dos MAP e piora na sustentação da parede vaginal anterior e no impacto da incontinência urinária na qualidade de vida ao longo dos três meses. / Introduction: Due to mechanical and hormonal factors, pregnancy and childbirth triggers changes that can lead to pelvic floor dysfunction (PFD). PFD studies in the immediate postpartum period are scarce and do unsystematic use of evaluation methods. Objective: To identify and evaluate the immediate, one month and three months postpartum PFD, comparing vaginal delivery (VD), elective cesarean (ECS) and cesarean indicating (ICS) during labor. Methods: This was a longitudinal observational study that assessed postpartum women after up to 48 hours (phase 1); one month (phase 2) and three months (phase 3). The study used the International Consultation on Incontinence Questionnaire (ICIQ-SF); Jorge-Wexner's Anal Incontinence (AI) score; the Visual Analogue Scale (VAS) for pelvic pain; the Pelvic Organ Prolapse Quantification System (POP-Q); and a Pelvic Floor Muscles (PFM) perineometer, as well as a structured questionnaire. Results: A total of 227 patients were assessed in phase 1 (141 had VD, 28 ICS and 58 ECS); 79 in phase 2 and 41 in phase 3. The ICIQ-SF, AI, VAS and perineometer index did not present significant differences in relation to the type of delivery. The distal point of the cervix presented more prolapse in VD. Conclusion: The type of delivery was not a significant factor for the development of postpartum PFD in the short term. The study found that there was physiological recovery of the functionality of PFM and worsening prolapse of the anterior vaginal wall and urinary incontinence over the three months.

The purpose of this research project was to elucidate the molecular interactions and detail the signaling pathways in obstetric pathologies. This work first seeks to understand inflammation related complications relevant to obstetrics. Prior research in our lab identified the implications of the receptor of advanced glycation end products (RAGE) during inflammatory response in the placenta. Current work identified the presence of DNA double-strand breaks (DNA-DSBs) in inflammation associated pregnancy complications of preeclampsia (PE) and preterm labor (PTL) and demonstrated the positive role of RAGE in repairing the damage. The confluent relevance of disrupted mitochondrial function and inflammation has been recognized in the etiology of numerous chronic diseases. Our current studies aim to understand the connections between energy metabolism and inflammation in pathologies of pregnancy complications. Previous research conducted in our laboratory has demonstrated the mediation of the Gas6/Axl pathway on the mechanistic target of rapamycin (mTOR), an important metabolic molecule. We observed the negative regulation of Gas6 treatment on the mTOR pathway and its negative effects on trophoblast cell invasion. In the current study looking at the aspect of energy regulation, we identified the activation of placental mTOR in gestational diabetes mellitus (GDM) and its decrease during PE and intrauterine growth restriction (IUGR). We further evaluated the regulation of mTOR on its downstream effector pyruvate kinase M2 (PKM2). We found that inhibition of mTOR decreased PKM2 activation; while PKM2 activation positively regulated trophoblastic invasion and rescued negative effects observed in our second-hand smoke IUGR murine model. Our work has opened a new direction of placental research, especially in pregnancy complications stemming from genomic instability. We also clarified details of mTOR and PKM2 meditated metabolic signaling that are crucial for future investigation on the dynamic metabolic regulation during pregnancy.

Während der Schwangerschaft vollziehen sich im Körper der Frau verschiedene Adaptionsmechanismen, um eine bestmögliche Versorgung für das heranwachsende Kind zu gewährleisten. Bei fortschreitender Gravidität entwickelt sich eine physiologische Insulinresistenz. Gelingt es den maternalen Betazellen des Pankreas‘ nicht, diese zu kompensieren, kann eine diabetische Stoffwechsellage bis hin zur Ausbildung eines Gestationsdiabetes (GDM) entstehen. Adipozytokine beeinflussen direkt lokale und periphere metabolische, endokrinologische sowie immunologische Prozesse. Inwieweit sie in der Gravidität eine Rolle spielen, ist bislang nicht hinreichend geklärt. In verschiedenen Studien wurde eine Beziehung zwischen den Fettgewebshormonen und der Glukosetoleranz in der Schwangerschaft nachgewiesen. Im Rahmen dieser Dissertation sollte eine Analyse zur Glukosetoleranz und zu Adipozytokinserumspiegeln bei Frauen unmittelbar nach der Entbindung vorgenommen werden. Ergebnisse oraler Glukosetoleranztests von gesunden Frauen 24 Stunden postpartal (n=65) wurden mit denen einer nicht-schwangeren, gesunden Kohorte (n=30) verglichen. Maternale und neonatale anthropometrische Daten wurden in Zusammenhang zu Adipozytokinen gestellt. Im Vergleich zu Frauen mit normaler Glukosetoleranz (NGT) postpartal konnten in dieser Studie signifikant verminderte Blutglukose – sowie nüchtern – Proinsulinspiegel in der nicht-schwangeren Kontrollgruppe nachgewiesen werden, wohingegen die nüchtern-C-Peptidspiegel erhöht waren. Weiterhin zeigten sich postpartal signifikant niedrigere Adiponektin-, aber höhere sOB-R- (soluble leptin receptor) sowie Leptinspiegel der NGT-Mütter im Vergleich zur Kontrollgruppe. Zusätzlich konnte eine Beziehung zwischen Adipozytokinserumspiegeln und Parametern der Glukosetoleranz bzw. Adipositas demonstriert werden. Daraus lässt sich die These ableiten, dass Frauen in der frühen Phase nach der Entbindung ähnliche biochemische Konstellationen wie beim metabolischen Syndrom, der gestörten Glukosetoleranz oder bei Störungen des Adipozytokinsystems aufweisen.:Bibliographische Beschreibung Abkürzungsverzeichnis 1 Einführung in die Thematik 1.1 Kohlenhydratstoffwechsel in der Schwangerschaft 1.1.1 Adipozytokine 1.1.1.2 Adiponektin 1.1.1.2 Leptin und der lösliche Rezeptor (sOB-R)1.1.1 1.2 Promotionsprojekt - Ziel und Fragestellung 1.2.3 Hintergrund und Fragestellung 1.2.3 Methoden 1.2.3 Ergebnisse 2 Publikation 3 Zusammenfassung und Interpretation der Arbeit 4 Literatur I Erklärung über das eigenständige Abfassen der Arbeit II Publikation III Dank

No description available.