4 p. / The saying “you are what you eat” takes on a new meaning when a woman learns she is expecting a baby. For the next several months, her growing baby’s health is directly dependent upon what she eats, and what she chooses to avoid. What is more, a woman’s diet during pregnancy has been shown to affect her child’s health long after she is no longer eating for two.

Background: Diabetes is a growing chronic disease that affects more than 29 million adults in the United States and 422 million adults globally. Women with a history of gestational diabetes (GDM) are identified to be at higher risk for developing subsequent type 2 diabetes mellitus (T2DM). The prevalence of GDM varies based on the data collection method, response rate, and diagnostic criteria. The aim of this study is to examine the association between history of GDM diagnosis and current T2DM status and how the relationship differs based on the participant’s age, race, and BMI. Methods: Data from the 2011-2012 and 2013-2014 National Health and Nutrition Examination Surveys (NHANES) were analyzed to conduct a cross-sectional study of 4,006 U.S. non-pregnant women ages 20 years and older with a history of prior pregnancy. The race/ethnicity of the participants include non-Hispanic Whites, non-Hispanic Blacks, Mexican Americans, non-Hispanic Asians, and "Other" variables. Univariate and multivariate logistic regression analyses were used to determine the association between history of GDM and current T2DM status stratified by age, race, and BMI. Results: Three hundred and fifteen subjects from a sample size of 4006 were found to have a history of GDM. Of the 315 participants with GDM, 111 (35.2%) were found to develop T2DM. After controlling for age, race, and body mass index (BMI), women with a history of GDM were found to be at greater odds of T2DM (OR=4.71; 95% CI: 3.52-6.28) compared to women without a history of GDM. A multivariate analysis was performed adjusting for other covariates such as age, race, BMI, and cholesterol. When stratified by participant age, women between the ages of 20-44 years with a history of GDM were linked with an increased risk of T2DM (OR= 3.02; 95% CI: 1.88-4.85). Overweight and obese women with a history of GDM have a 2.5-fold risk of developing T2DM (OR=2.51; 95% CI: 1.49-4.23). Discussion: This study provides further understanding and awareness on the role of GDM during the subsequent risk for T2DM. Our study shows women between the ages of 20 and 44 years and with elevated BMIs (25 ≥ kg/m2) are at increased risk of developing subsequent T2DM. Findings suggest the need for health promotion and prevention efforts towards the populations at risk. Early intervention post-pregnancy and education may help prevent women with a history of GDM from developing T2DM.

Pendant la grossesse, les aquaporines (AQPs) exprimées au sein des membranes fœtales sont essentielles pour assurer l’homéostasie du volume de liquide amniotique (LA), mais leur régulation par l’insuline n’a jamais été explorée chez les femmes diabétiques.Le but de notre étude était de préciser le rôle des AQPs 1, 3, 8 et 9 au sein des membranes fœtales chez des parturientes diabétiques et d’étudier la régulation de leur expression par l’insuline.A partir des 129 membranes fœtales, réparties selon 4 populations (36 témoins, 35 diabètes de type 1 (DT1), 17 diabètes de type 2 (DT2) et 41 diabètes gestationnels (DG)), nous avons établi un profil d’expression qualitatif et quantitatif des gènes des AQPs. Dans un second temps, nous avons étudié la régulation par l’insuline de l’expression des AQPs 3 et 9 au sein d’explants d’amnion et de chorion. L’expression ARN et protéique des AQPs au sein de nos différents fragments de membranes fœtales a été étudiée par RT-PCR quantitative et ELISA. Des membranes fœtales issues de grossesses non pathologiques, séparées en ses 2 feuillets (amnion et chorion), ont été utilisées pour étudier la régulation de l’expression des gènes des AQPs 3 et 9 par l’insuline ainsi que la voie de signalisation de l’insuline au sein de l’amnion. Un test au glycérol tritié a permis l’étude fonctionnelle de l’insuline sur les AQPs. Un inhibiteur de la phosphatidyl-inositol 3-kinase (PI3K) est utilisé pour analyser le signal intracellulaire de l’insuline.L’expression du gène de l’AQP 3 est significativement plus faible dans les groupes DT2 et DG. Au sein d’explants de membranes fœtales non diabétiques, il a été observé au sein de l’amnion (mais pas du chorion), une répression significative par l’insuline de l’expression ARN et protéique des gènes AQPs 3 et 9 qui est bloquée par l’inhibiteur de PI3K. Au sein des membranes fœtales, la répression de l’AQP 3 observée in vivo, est permise par l’hyperinsulinisme connu des patientes atteintes de DT2 ou de DG. / During pregnancy, aquaporins (AQPs) expressed in fetal membranes are essential for controlling the homeostasis of the amniotic volume, but their regulation by insulin was never explored in diabetic women.The aim of our study was to investigate the involvement of AQP 1, 3, 8, and 9 expressed in fetal membranes in diabetic parturient women, and the control of their expression by insulin.From 129 fetal membranes in 4 populations, (controls, type 1 (T1D), type 2 (T2D) and gestational diabetes (GD)), we established an expression AQPs profile. In a 2nd step, the amnion was used to study control of the expression and functions of AQPs 3 and 9 by insulin.The expression of transcripts and proteins of AQPs was studied by qRT-PCR and ELISA. We analysed the regulation by insulin of the expression of AQPs 3 and 9 in the amnion. A tritiated glycerol test enabled us to measure the impact of insulin on the functional characteristics. Using an inhibitor of phosphatidylinositol 3-kinase (PI3K) we analysed the insulin intracellular signaling pathway.Expression of AQP3 protein was significantly weaker in groups T2D and GD. In non-diabetic fetal membranes, we showed for the amnion (not for the chorion) a significant repression by insulin of the ARN expression of AQPs 3 and 9, which was blocked by PI3K inhibitor.In fetal membranes, the repression of AQP3 protein expression and functions observed in vivo is allowed by the hyper-insulinism described in pregnant women with T2D or GD.

Pregnancies complicated with diabetes mellitus (DM) are associated with poor maternal and fetal outcomes, such as birth trauma, fetal overgrowth (macrosomia) and programming of the fetus to develop metabolic syndrome in adult life. Maternal hyperglycemia is thought to contribute to fetal macrosomia, however the role of the placenta in these pregnancies is incompletely understood, therefore we aimed to investigate the specific consequences of high glucose on placental metabolism. To achieve this aim an in vitro model of placental exposure to high glucose was developed. This model was used with the aim of analysing how high glucose alters the transcriptome and metabolome of these cells, using a systems biology approach to identify candidate functional pathways which may be altered in placenta as a result of hyperglycemia. These candidate functional pathways were validated in an ex vivo model of placenta exposed to high glucose and in placental tissue from pregnancies complicated by DM. A trophoblast cell line (BeWo) was cultured in low (5 mM) and high (12 mM or 25 mM) D-glucose conditions for 48 hours. Transcriptomic and metabolomic analysis of these cells was performed using microarrays, and gas- and liquid-chromatography-mass spectrometry, respectively. Transcript and metabolite changes were independently analysed and integrated, using network analysis. From the integrated analysis of the ‘omic datasets, β-fatty acid oxidation (β-FAO), purine metabolism, phosphatidylinositol/PI3K phosphate pathway and lipid metabolism, were identified as candidates for further study. Changes within the PI3K pathway and lipid metabolism/β-fatty acid oxidation were validated in an ex vivo placental explant model of high glucose and in placental tissue from women with DM, compared to uncomplicated pregnancies. mRNA, protein expression and protein activation of key molecules within the PI3K pathway were not significantly altered in placenta as a response of high glucose ex vivo or DM in vivo. The second candidate functional pathway, lipid metabolism, has previously been implicated in association with placental dysfunction in pregnancies complicated by DM. Placental fatty acid transporter and lipase protein expression, as well as, relative abundance of different fatty acids were unaltered in response to high glucose or DM. High glucose levels increased triglyceride levels within the placenta, indicating reduced rates of β-FAO. The effect of high glucose could be ameliorated using a PPARα agonist. This may provide a novel therapeutic intervention to prevent excess esterification of fatty acids to triglycerides in maternal diabetes, which may in turn influence fetal growth. This study illustrates how a systems biology approach can be used to identify novel candidate functional pathways that are altered within the trophoblast in response to high glucose. Thus, improving understanding of placental dysfunction in these pregnancies and providing novel candidate pathways for future study, which may represent potential therapeutic targets for intervention of fetal macrosomia in pregnancies complicated by DM.

Magister Pharmaceuticae - MPharm / Gestational diabetes mellitus (GDM) is a condition that affects pregnant women and is one of the most common complications related to pregnancy. According to the World health organisation (WHO), the usual window for diagnosing GDM is between 24 and 28 weeks of gestation and the primary aim of diagnosing gestational diabetes is to identify women and infants at risk of short- or longer-term adverse outcomes. Recent results from the hyperglycaemia and adverse pregnancy outcome (HAPO) study have suggested that even mild levels of hyperglycaemia can have adverse effects on foetal outcomes but there are uncertainties about the prevalence of these outcomes in GDM diagnosed according to the latest WHO 2013 guideline and/or IADPSG 2010 criteria in diverse populations. GDM prevalence has been studied by different researchers, but the prevalence of adverse foetal outcomes in GDM diagnosed based on the latest WHO 2013 guideline and/or IADPSG 2010 criteria have not yet been explored except for the data published by the HAPO study. Due to the lack of sufficient knowledge on foetal outcomes in GDM, this study was conducted to review the evidence on the prevalence of adverse foetal outcomes in GDM diagnosed according to WHO 2013 guideline and/or the IADPSG 2010 criteria. Different databases including PubMed, Science Direct, Google Scholar and CINAHL as well as bibliographic citations were searched using a well-formulated search strategy to find the relevant observational studies (prospective/retrospective cohort and case-control) using explicit inclusion and exclusion criteria. The following search terms were used, “gestational diabetes”, “pregnancy”, “adverse fetal outcomes” and “adverse foetal outcomes”. The findings of this study were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the obtained data analysed using MetaXL ® version 5.3. This review was registered online on PROSPERO, the International prospective register of systematic reviews (registration number: CRD42020155061). Fifteen studies with 88,831 pregnant women (range: 83-25,543 participants) from 12 countries around the world were identified, with a wide variation in the prevalence of foetal outcomes in GDM using the stipulated criteria. These studies were unevenly distributed geographically as six of them were conducted in Asia, four in Europe, four in North America, one in Australia and none in Africa, Antarctica and South America. A meta-analysis found that the overall prevalence of foetal outcomes ranged from 1% (perinatal mortality) to 11% ( large for gestational age). The finding is limited due to the paucity of data on the prevalence of foetal outcomes in GDM. However, more studies using these criteria in low- and middle- income countries (LMICs) are needed by health care providers, to inform practice and allocate resources for control of GDM and its adverse foetal outcomes in diverse settings and ethnic groups, especially in LMICs.

Thesis (MPH.) -- University of Limpopo, 2020 / The purpose of this study was to determine the prevalence of gestational diabetes mellitus (GDM) and the associated risk factors in the Greater Giyani Area, Mopani District. Quantitative cross-sectional descriptive study was conducted to determine the prevalence rate and risk factors of GDM. Data was collected using questionnaire and data entry form. One hundred and one (101) pregnant women who were attending antenatal clinic visits at Nkhensani Hospital, Nkhensani Gateway Clinic and Giyani Healthcare Centre participated in the study. The SPSS programme was used and p-value of <0.05 was considered significant. The study found that the prevalence of GDM in the area was 1.9%. Pregnant women above 30 years with secondary education, employed, obese and at gestational age of 31-35 weeks were more likely to present with GDM. A family history of diabetes was significantly associated with development of GDM. In conclusion, the universal screening approach for GDM needs to be adopted by all health institutions.

Gestational diabetes mellitus (GDM ) is a disease that appears during pregnancy due to an insulin resistance. GDM is associated with increased risks for complications both to the mother and the child during pregnancy. These risks include conditions such as neonatal macrosomi and hypoglycemia for the child. This leads to increased risk for cesarean section and birth injuries. GDM can be treated with a changed diet supported with exercise. If the blood glucose levels still remain high, insulin or metformin medication can be introduced to treat the patient. Metformin is a safe and effective anti-diabetic drug and it is used as a treatment for GDM. Since the treatment during GDM varies, the effect of insulin versus metformin was examined. The aim of this litterature study was to compare the treatment with metformin versus insulin and to investigate the differences between the two drugs in the treatment of GDM. The medical databases PubMed and Google Scholar were used to search for clinical studies that compare the effects of the two treatments. Four studies were selected for this litterature study. The results in this study indicated that both insulin and metformin are effective as  glucose lowering drugs in the treatment of GDM. All patients do not respond to metformin and therefore insulin may be preferable in the treatment of some patient. Both insulin and metformin lead to better glycemic control in GDM patients. Both drugs are safe and effective but metformin has several advantages. The cost is low, it is easier to use and leads to fewer cases of hypoglycemia compared to insulin, even though all patients do not respond to metformin, it is considered a good alternative.

Introduction: Gestational diabetes mellitus (GDM) is a significant public health concern, due to its association with short- and long-term complications in both mothers and offspring. DNA methylation and single nucleotide polymorphisms (SNPs) offer potential to serve as molecular biomarkers, which may lead to improved detection of GDM with positive effects on health outcomes. Aim: The aim of this study was to investigate whether DNA methylation and SNPs are associated with GDM and may offer potential as molecular biomarkers for GDM in South Africa (SA). Methods: This study followed a two-pronged approach. Firstly, literature searches were conducted to collate and synthesise all published articles reporting on the prevalence of GDM in SA, the screening and diagnostic strategies used, and the current status of DNA methylation and SNPs as biomarkers for GDM. Secondly, we conducted experiments to investigate global (n=201), genome-wide (n=24) and gene-specific DNA methylation (n=286) of the adiponectin gene (ADIPOQ) in whole blood of women with and without GDM, using an Enzyme-Linked Immunosorbent Assay, a methylationEPIC BeadChip Array and pyrosequencing, respectively. In addition, genotype and allele frequencies of ADIPOQ rs266729 and rs17300539, and methylenetetrahydrofolate reductase (MTHFR) rs1801133 were determined, using quantitative real-time PCR (n=449) and DNA sequencing for validation. Results: The literature search showed that the prevalence of GDM in SA has increased over the years. Furthermore, it showed that the lack of uniformity in screening and diagnosis between and within countries hamper the accurate detection of GDM. Lastly, the literature search identified several studies that support the use of DNA methylation and SNPs as potential biomarkers for GDM. Experimentally, we showed no differences in global DNA methylation between GDM and non-GDM groups. Interestingly, global DNA methylation levels were 18% (p=0.012) higher in obese compared to non-obese pregnant women. Genome-wide methylation analysis identified 1046 differentially methylated CpG sites (associated with 939 genes) (Cut-off threshold: M>0.06 and p<0.01). Among the top five CpG sites identified, one CpG mapped to the calmodulin-binding transcription activator 1 (CAMTA1) gene, which has been shown to regulate insulin production and secretion. Two CpG sites (-3410: p=0.048 and -3400: p=0.004) in the ADIPOQ promoter were hypomethylated during GDM in HIV negative, but not in HIV positive women. Lastly, no association between the ADIPOQ and MTHFR polymorphisms and GDM was observed in our population. Conclusion: To our knowledge, this is the first study to investigate the association between DNA methylation or ADIPOQ (rs266729 and rs17300539) and MTHFR (rs1801133) polymorphisms and GDM in SA. Findings suggest that gene-specific, but not global methylation nor SNPs rs266729, rs17300539 and rs1801133, may offer potential as molecular biomarkers of GDM in this population. Future longitudinal studies in larger samples that include both HIV negative and positive pregnant women are warranted to explore the candidacy of DNA methylation as molecular biomarkers for GDM. / Thesis (PhD)--University of Pretoria, 2019. / National Research Foundation (NRF) of South Africa, Thuthuka Grant (unique grant no. 99391). / South African Medical Research Council (SAMRC) / Obstetrics and Gynaecology / PhD / Unrestricted

Bakgrund: Diagnosen graviditetsdiabetes innebär en glukosintolerans vilket kan ge stora konsekvensersom komplikationer vid födsel, makrosomi eller diabetes typ 2. Riskfaktorerna för att fådiagnosen är bland annat högt BMI, ålder &gt;35 år samt låg fysisk aktivitetsnivå. Behandlingensom ges idag är råd om kost och träning, vid behov kan även läkemedel förskrivas. Syfte: Att sammanställa det nuvarande vetenskapliga underlaget vad gäller fysisk aktivitet för attförebygga uppkomst av diabetes hos gravida kvinnor i riskzonen för att utvecklagraviditetsdiabetes. Metod: Detta arbete är en systematisk litteraturstudie av randomiserade kontrollerade studier, somidentifierades via databaserna PubMed och Scopus. Granskning av risk för snedvridningbedömdes med TESTEX och tillförlitligheten för det sammanvägda resultatet bedömdes meden lokal mall från Uppsala universitet. Resultat: Åtta artiklar inkluderades i litteraturöversikten. Sju artiklar fick mellan 10-13 poäng efterTESTEX granskningen. En artikel uppnådde inte gränsvärdet för tillräcklig kvalité för attinkluderas i det sammanvägda resultatet. De sju artiklar med lägst risk för snedvridningvisade att träning inte hade någon signifikant effekt för att kunna förebygga uppkomsten avgraviditetsdiabetes. Tillförlitligheten till det sammanvägda resultatet bedömdes som låg. Slutsats: Baserat på resultaten från denna översikt konstateras att träning inte har en signifikant effektpå att förebygga graviditetsdiabetes för kvinnor med högt BMI alternativt låg fysiskaktivitetsnivå. Dock, på grund av den låga tillförlitligheten i de sammanvägda resultaten,behövs mer forskning inom detta område. / Background: The diagnosis of gestational diabetes implies glucose intolerance, which can have significantconsequences such as birth complications, macrosomia, or type 2 diabetes. Risk factors fordeveloping gestational diabetes include a high BMI, age &gt;35 years and low physical activitylevels. The current treatment provided involves advice on diet and exercise, and if necessary,medication can also be prescribed. Objective: To gather the current scientific evidence regarding the prevention of gestational diabetes withphysical activity for women at risk of developing gestational diabetes. Methods: This work was a systematic literature review of randomized controlled trials obtained throughthe databases PubMed and Scopus. Review of the risk of bias was assessed using TESTEX,and the reliability of the aggregated result was evaluated using a local template from UppsalaUniversity.  Results: Eight articles were included in the literature review. Seven articles scored between 10-13points after the TESTEX evaluation. One article did not reach the threshold for sufficientquality to be included in the combined results. The seven articles with the lowest risk of biasindicated that exercise did not have a significant effect in preventing the onset of gestationaldiabetes. However, the reliability of the aggregated result was assessed as low. Conclusions: Based on the findings from this review, it is observed that exercise does not have a significanteffect in preventing gestational diabetes for women with either high BMI or low physicalactivity levels. However, due to the low reliability of the combined results, more research isneeded in this area.

Objectif : Établir le profil psychosocial des femmes enceintes de l'Estrie et évaluer de façon préliminaire si ce profil diffère parmi les grossesses avec issues défavorables. Méthode. Cohorte prospective de 120 femmes enceintes, rencontrées à deux reprises (10-20 et 25-30 semaines), entre août 2004 et mars 2006. Il s'agit d'un questionnaire auto-administré des données démographiques, anthropométriques, des facteurs de risques biomédicaux, ainsi qu'un profil psychosocial comportant 6 dimensions: stress psychologique perçu, ennuis quotidiens, détresse psychologique, locus de contrôle, soutien social, traumatismes dans l'enfance. Les paramètres psychosociaux sont présentés en moyennes ou pourcentages. Le profil psychosocial est comparé entre les grossesses normales et anormales avec les tests t de Student ou le test de Mann Whitney, lorsque approprié. Résultats. Trente trois grossesses (27,5%) ont présenté des issues défavorables (prématurité, restriction de croissance intra-utérine, hypertension gestationnelle, diabète gestationnel). L'analyse du profil psychosocial révèle un score de stress psychologique perçu plus élevé entre 10-20 semaines chez les femmes avec issues défavorables de grossesse (score : 34,2 « 12,3 ; P < 0,01) et chez les femmes avec prématurité (score : 36,1 « 11,2 ; P < 0,02) comparativement à celui des femmes avec grossesses normales (score : 28,6 « 9,6). Par ailleurs, les 5 autres dimensions ne semblaient pas différentes selon les issues de grossesse. Conclusion. Ces résultats préliminaires suggèrent une piste possible reliant la perception de stress maternel durant la grossesse et certaines issues défavorables de grossesse, dont l'accouchement prématuré.