Gestational diabetes mellitus (GDM) is a common complication of pregnancy and population health studies have linked it to impaired cognitive performance in the offspring. GDM triggers inflammatory responses, which can critically affect development of neuronal circuitry. We hypothesized that GDM promotes inflammatory responses in the fetus that can disturb fine-tuning of neuronal networks during early development, resulting in lifelong impaired cognitive functions. The cognitive performance of 15 week old offspring exposed to diet induced GDM were assessed. The brain tissue of the 15 week old and neonatal (E20) offspring were analyzed by immunohistochemistry, western blot, and cytokine assay. Cultured microglial responses to elevated glucose and/or fatty acid levels mimicking GDM associated diabetic conditions were analyzed. Our data reveals chronic neuroinflammation in GDM offspring, which combined with deregulation of microglial functions may explain hippocampal CA1 layer neuronal derangement and synaptic degradation that correlates with impaired cognitive performance of GDM offspring. / October 2016

Gestational diabetes mellitus (GDM) negatively affects the health of both mothers and babies, and is the most common pregnancy complication in the United States. Many dietary modification programs for pregnant women diagnosed with GDM rely on a one-size-fits-all approach to menu planning. The purpose of this project was to develop a diet modification program for GDM management using a patient-centered approach. The project objective was to develop the policies, procedures, and supporting documents needed to implement a successful GDM management program for pregnant women receiving antenatal care at an obstetrical clinic. The developed program incorporated strategies for clinic nursing staff to involve pregnant patients and their family members in the planning of individualized daily menus addressing social, motivational, and economic factors. Patient understanding of diet management will be evaluated through the administration of written pre and post-tests, which were included with the program materials. Long term program evaluation will be determined through the tracking of maternal weight gain and infant birth weights. This program has the potential to contribute to positive social change through the reduction of complications resulting from inadequately managed gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is the most common metabolic complication in pregnancy and is associated with substantial maternal and neonatal morbidity. The standard of care for GDM in most developed countries is universal mid- to late- pregnancy (24-28 weeks gestation) glucose testing. While earlier diagnosis and treatment could improve pregnancy outcomes, tools for early identification of risk for GDM are not commonly used in practice. Existing models for predicting GDM risk within the first trimester of pregnancy based on maternal risk factors perform only modestly in the clinical setting. Heavy reliance on history of GDM to predict GDM development in the current pregnancy prevents these tools from being applicable to nulliparous women (i.e., women who have never given birth). In order to offer timely preventive intervention and enhanced antenatal care to nulliparous women, we need to be able to accurately identify those at high risk for GDM early in pregnancy. Data from the California Office of Statewide Health Planning and Development Linked Birth File was used to address three aims: 1) improve early pregnancy prediction of GDM risk in nulliparous women through development of a risk factor-based model, 2) conduct a systematic review and meta-analysis assessing the relationship between first trimester prenatal screening biomarker levels and development of GDM, and 3) determine if the addition of first and second trimester prenatal screening biomarkers to risk factor-based models will improve early prediction of GDM in nulliparous women. We developed a clinical prediction model including five well-established risk factors for GDM (race/ethnicity, age at delivery, pre-pregnancy body mass index, family history of diabetes, and pre-existing hypertension). Our model had moderate predictive performance among all nulliparous women, and performed particularly well among Hispanic and Black women when assessed within specific racial/ethnic groups. Our risk prediction model also showed superior performance over the commonly used American College of Obstetricians and Gynecologists (ACOG) screening guidelines, encouraging the prompt incorporation of this tool into preconception and prenatal care. Biomarkers commonly assessed in prenatal screening have been associated with a number of adverse perinatal and birth outcomes. However, reports on the relationship between first trimester measurements of prenatal screening biomarkers and GDM development are inconsistent. Our meta-analysis demonstrated that women who are diagnosed with GDM have lower first trimester multiple of the median (MoM) levels of both pregnancy associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (free β-hCG) than women who remain normoglycemic throughout pregnancy. Findings from our meta-analysis suggested that incorporation of prenatal screening biomarkers in clinical risk prediction models could aid in earlier identification of women at risk of developing GDM. Upon linkage of California Office of Statewide Health Planning and Development Linked Birth File and California Prenatal Screening Program records, we found that decreased levels of first trimester PAPP-A, increased second trimester unconjugated estriol, and increased second trimester dimeric inhibin A were associated with GDM development in nulliparous women. However, the addition of these biomarkers in clinical models did not offer improvements to the clinical utility (i.e., risk stratification) of models including maternal risk factors alone. Our findings demonstrate that incorporation of maternal risk factors in a clinical risk prediction model can more accurately identify nulliparous women at high risk for GDM early in pregnancy compared to current standard practice. The maternal characteristics model we developed is based on clinical history and demographic variables that are already routinely collected by clinicians in the United States so that it may be easily adapted into existing prenatal care practice and screening programs. Future work should focus on evaluating the clinical impact of model implementation on maternal and infant outcomes as well as financial costs to the health care system.

Gestational diabetes (GDM) is a potentially serious disorder requiring timely diagnosis and management to prevent adverse maternal and fetal outcomes. Of increasing concern today, when treating the woman with GDM, is the need to provide every woman with an intensive management plan to optimise the likelihood of favourable pregnancy outcomes. Early identification of those women with GDM who require insulin therapy in addition to diet therapy would be beneficial in the planning and standardisation of clinical management protocols, to enhance pregnancy outcomes and increase cost benefits with improved allocation of resources. The aim of this study was to evaluate the ability of the fasting plasma glucose level (FPG) at diagnosis to predict an increased risk to the fetus and the need for insulin therapy in a pregnancy complicated by GDM. A prospective longitudinal study design and recruitment by convenience sample was used. Data were obtained from 327 women and their babies. Diagnosis of GDM was made by a 75 gram oral glucose tolerance test (OGTT) using Australasian Diabetes in Pregnancy Society (ADIPS) criteria with the exception of seven women diagnosed on a blood glucose level >11.1mmol/l. Following consent of the women data were collected by a self report questionnaire and the medical record system at three points; at first intervention, following delivery and at the postpartum OGTT. Demographic, social, medical, maternal and neonatal outcome data were collected. The management protocol was similar for all of the women. Following nutritional intervention any woman who could not meet the glycemic targets of <= 5mmol/l fasting and/or <= 6.5mmol/l two hours postprandial was commenced on insulin therapy. The women had a mean age of 32 years, body mass index (BMI) of 25.7 and parity of 2 (range 1-12). Diagnosis was made at an average of 30 weeks and 70 women required insulin therapy with a mean dose of 34 IU per day, commencing at a mean of 31 weeks gestation. Mean birthweight was 3400G. Of the babies 12% were >4000G. Congenital abnormalities occurred in 3%, neonatal morbidities in 2% and there was 1 death in utero. Logistic regression analysis found the following significant associations: Increasing maternal BMI was related to increasing FPG levels at diagnosis and the requirement of higher insulin doses. There was a negative linear relationship to weight gain. Ethnicity was associated with maternal BMI and ethnicity with BMI was associated with birthweight in the specific ethnic group. BMI with insulin therapy as a covariate and the FPG value at OGTT were predictive of persistent glucose intolerance in 14% of women postpartum. Each value of the OGTT was a significant predictor of the need for insulin therapy as a function of the week of gestation. The FPG level was the statistical model of best fit. A 50% probability for requiring insulin was reached with a FPG at diagnosis of 4.0 mmol/l if tested at 10 weeks gestation, 5.1mmol/l at 20 weeks and 6.1 mmol/l at 30 weeks (p<.001). These results support the substantive research aim of the study. The model has the power to predict the probability (risk) of requiring insulin therapy based on the maternal FPG level at the OGTT according to the week of gestation. The study results demonstrate that glucose intolerance is linked to a number of adverse maternal and fetal outcomes in a continuous and graded fashion. The degree of reversibility of maternal and fetal risk through therapeutic interventions such as nutrition therapy, blood glucose monitoring, exercise and active patient participation aimed at improving glucose tolerance is unknown. Therefore, the rationale for, and feasibility of, new treatment strategies such as the application of this statistical model as a management approach require large scale randomised intervention studies, oriented toward measuring maternal and fetal outcomes amongst different populations.

Gestational diabetes, a common medical complication in pregnancy, may lead to severe fetal consequences if left untreated. A major concern with the use of antidiabetic drugs in pregnancy is the potential for placental transfer and fetal toxicity. The presence of endocytic pathways and several ABC transporter proteins has been demonstrated in the human placenta and are believed to play an important role in determining fetal exposure to drugs used in pregnancy. The objective of this thesis is to investigate the safety and transfer of the oral hypoglycemic agent, glyburide, and the new long acting insulin analog, insulin glargine, across the human placenta. The oral antidiabetic, glyburide, has been shown to be actively effluxed across the placenta in the fetal to maternal direction. The transport of glyburide in the presence of a breast cancer resistance protein (BCRP) inhibitor was investigated in the dually perfused human placenta model. The results of the perfusion studies indicate that BCRP plays a role in protecting the fetus from the accumulation of glyburide. Subsequently, cellular studies were carried out to determine the effect of the naturally occurring single nucleotide polymorphism within the coding region of BCRP (C421A/Q141K) on glyburide transport. Results suggest that glyburide transport may be reduced in the presence of the Q141K polymorphism. While insulin remains as the gold standard, the potential for maternal hypoglycemia with insulin injection has resulted in the development of insulin analogs. Insulin glargine, a human insulin analog, has a long half life with no pronounced peak when compared to currently used NPH insulin. Human placental perfusion experiments examining the extent and rate of transfer of insulin glargine across the placenta demonstrated that, at therapeutic concentrations, insulin glargine does not cross the placenta to a measurable extent. To further determine the fetal safety of insulin glargine therapy compared with NPH insulin, a systematic review and meta-analysis were performed. No evidence was identified for increased adverse fetal outcomes with the use of insulin glargine during pregnancy. Overall, the results of this research serve to provide improved treatment options for women with diabetes in pregnancy.

Gestational diabetes, a common medical complication in pregnancy, may lead to severe fetal consequences if left untreated. A major concern with the use of antidiabetic drugs in pregnancy is the potential for placental transfer and fetal toxicity. The presence of endocytic pathways and several ABC transporter proteins has been demonstrated in the human placenta and are believed to play an important role in determining fetal exposure to drugs used in pregnancy. The objective of this thesis is to investigate the safety and transfer of the oral hypoglycemic agent, glyburide, and the new long acting insulin analog, insulin glargine, across the human placenta. The oral antidiabetic, glyburide, has been shown to be actively effluxed across the placenta in the fetal to maternal direction. The transport of glyburide in the presence of a breast cancer resistance protein (BCRP) inhibitor was investigated in the dually perfused human placenta model. The results of the perfusion studies indicate that BCRP plays a role in protecting the fetus from the accumulation of glyburide. Subsequently, cellular studies were carried out to determine the effect of the naturally occurring single nucleotide polymorphism within the coding region of BCRP (C421A/Q141K) on glyburide transport. Results suggest that glyburide transport may be reduced in the presence of the Q141K polymorphism. While insulin remains as the gold standard, the potential for maternal hypoglycemia with insulin injection has resulted in the development of insulin analogs. Insulin glargine, a human insulin analog, has a long half life with no pronounced peak when compared to currently used NPH insulin. Human placental perfusion experiments examining the extent and rate of transfer of insulin glargine across the placenta demonstrated that, at therapeutic concentrations, insulin glargine does not cross the placenta to a measurable extent. To further determine the fetal safety of insulin glargine therapy compared with NPH insulin, a systematic review and meta-analysis were performed. No evidence was identified for increased adverse fetal outcomes with the use of insulin glargine during pregnancy. Overall, the results of this research serve to provide improved treatment options for women with diabetes in pregnancy.

Women with gestational diabetes (GD) are at higher risk of developing type 2 diabetes (DM) after delivery compared to those without GD. Numerous studies in the general population have identified that adoption of healthy lifestyles can prevent DM; however limited research has focused on women with GD. The purpose of this randomized pilot study was to determine the effectiveness of an educational intervention of SUGAR (Start Understanding Gestational Diabetes and Risk of Type 2 Diabetes), on women’s perceived risk of developing DM, knowledge of DM, self-efficacy to adopt healthy lifestyle behaviors and adoption of healthy lifestyle behaviors after childbirth among women with GD. A total of 23 women (mean age of 29.7, SD=3.9), 18 in SUGAR group and 5 in control group (CG) completed self-reported standardized questionnaires (Risk Perception Survey for Developing Diabetes adapted for women with GD; Self-Rated Abilities for Health Practices; Health Promotion Lifestyle Profile II; General Sleep Disturbance Scale; and Demographic Questionnaire) at baseline (third trimester) and post-test (postpartum 6-8 weeks). Intervention was given post the baseline data collection with a booster session at 2-4 weeks postpartum. The women in CG received attention control treatment. Study participants were obese (BMI M=33.1, SD=7.7) and a majority had a family history of DM. Findings showed that self-efficacy was the single significant predictor and accounted for 22% of the variance of healthy lifestyle behaviors. Participants had a clinical significant sleep disturbance during both pregnancy and postpartum. At baseline, poor sleepers reported a lower self-efficacy. The intervention significantly increased DM knowledge for women in the SUGAR group; however, not for perceived risk, self-efficacy nor healthy lifestyle behaviors. There was no difference between groups for postpartum glucose screening rates with only 39% receiving recommended testing. Future research needs to focus on prevention programs and center on self-efficacy, postpartum glucose screening, improve sleep, and adoption of healthy lifestyle behaviors. To ensure a better preventive care for GD women, education provided for both patients and health care provider is needed.

The purpose of this biobehavioral study was to explore relationships between psychosocial stressors of acculturation, acculturative stress, and metabolic markers of leptin and adiponectin in Mexican American women with and without gestational diabetes mellitus (GDM). A case control design was used for this secondary analysis which included a sample of 38 pregnant women with GDM and 38 healthy controls without GDM, who were matched on age and BMI status. Subjects completed two surveys—the Multidimensional Acculturation Scale II (MASII) and the Multidimensional Acculturative Stress Inventory (MASI)—which measured acculturation and acculturative stress. Descriptive statistics, Pearson r correlations, and independent sample t-tests were used to analyze the data. The results from this study indicated that significant relationships do exist between some of the variables of interest; however, there were no overall significant differences found between women with and without gestational diabetes. These mixed results may be an indicator of a need to further explore these concepts. / text

Made available in DSpace on 2014-06-11T19:32:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-10-20Bitstream added on 2014-06-13T18:44:46Z : No. of bitstreams: 1 negrato_ca_dr_botfm_prot.pdf: 898163 bytes, checksum: a56403a143501d6e1f412e9ff5d74684 (MD5) / Fundação para o Desenvolvimento Médico e Hospitalar (Famesp) / Em 1988, Reaven descreveu a síndrome X, uma junção de diversos fatores de risco para as doenças cardiovasculares, sendo a resistência à insulina o ponto de partida para o estabelecimento de tais fatores. Várias denominações foram dadas a este grupo de comorbidades e hoje ela é conhecida como Síndrome Metabólica. Seu estudo tem sido dificultado pela ausência de consenso na sua definição. Sua prevalência varia de acordo com o critério diagnóstico utilizado e com as características da população estudada, sendo mais encontrada em portadores de obesidade central. A prevalência em mulheres varia de 10,7% a 40,5%, e é um preditor para o desenvolvimento de complicações cardiovasculares, estando associada a duas importantes entidades nosológicas bastante estudadas em ginecologia e obstetrícia: a síndrome dos ovários policísticos e o diabetes gestacional. Embora não façam parte dos critérios diagnósticos, várias condições clínicas e fisiopatológicas estão freqüentemente a ela associadas, tais como: acantose nigricans, doença hepática gordurosa não-alcoólica, microalbuminúria, estados pró trombóticos (elevação dos níveis de PAI-1 e fibrinogênio), estados pró- inflamatórios (elevação dos níveis de IL-6, TNF-a, resistina e PC-R), disfunção endotelial e hiperuncemia. Os autores fazem uma revisão sobre o diagnóstico laboratorial e os fatores ligados a SM evidenciando que a Critósos diagnósticos atuais da síndrome metabólica gravidez é um modelo da SM compensada e sugerem que o diabetes gestacional e a hipergilcemia materna diária devam ser acrescentados aos critérios diagnósticos. / In 1988, Reaven described the Syndrome X, a junction of several risk factors for cardiovascular diseases, being the insulin resistance the set point for the establishment of such factors. Many denominations were given to this group of co-morbidities and today it is known as metabolic syndrome. lts study has been difficult by the absence of a consensus for its definition. lts prevalence vanes according to the diagnostic criterion used and with the characteristics of the studíed population, being found mainly in people with central obesity. The prevalence in women varies from 10.7% to 40.5%, and it is a predictor of cardiovascular complications associated with two important nosologic entities concerned with gynecology and obstetrics: the polycystic ovaries syndrome and gestational diabetes. A variety of clinical and physiopathoiogical conditions are frequently associated to it. These are: acanthosis nigricans, non alcoholic fatty tiver disease, microalbuminuria, prothrombotic states (elevation of PAI-1 and fibrinogen leveIs), proinflammatory states (elevation of IL-6, TNF-a, resistin and C-RP leveis), endothelial dysfunction and hyperuricemia. The authors make a revision on the laboratorial diagnosis and the factors Iinked to the metabolic syndrome and attest that pregnancy is a counterbalanced model of the syndrome Critérios diagnósticos atuaiS da 5ifldrOme metabólica and suggest that gestational diabetes and diurnal maternal hyperglycemia should be added to the diagnostic criteria.

Orientador: Marilza Vieira Cunha Rudge / Banca: Marilza Vieira Cunha Rudge / Banca: Domingos Augusto Malerbi / Banca: Marcos Antonio Tambacia / Banca: Angela de Azevedo Jacób Reichelt / Resumo: Em 1988, Reaven descreveu a síndrome X, uma junção de diversos fatores de risco para as doenças cardiovasculares, sendo a resistência à insulina o ponto de partida para o estabelecimento de tais fatores. Várias denominações foram dadas a este grupo de comorbidades e hoje ela é conhecida como Síndrome Metabólica. Seu estudo tem sido dificultado pela ausência de consenso na sua definição. Sua prevalência varia de acordo com o critério diagnóstico utilizado e com as características da população estudada, sendo mais encontrada em portadores de obesidade central. A prevalência em mulheres varia de 10,7% a 40,5%, e é um preditor para o desenvolvimento de complicações cardiovasculares, estando associada a duas importantes entidades nosológicas bastante estudadas em ginecologia e obstetrícia: a síndrome dos ovários policísticos e o diabetes gestacional. Embora não façam parte dos critérios diagnósticos, várias condições clínicas e fisiopatológicas estão freqüentemente a ela associadas, tais como: acantose nigricans, doença hepática gordurosa não-alcoólica, microalbuminúria, estados pró trombóticos (elevação dos níveis de PAI-1 e fibrinogênio), estados pró- inflamatórios (elevação dos níveis de IL-6, TNF-a, resistina e PC-R), disfunção endotelial e hiperuncemia. Os autores fazem uma revisão sobre o diagnóstico laboratorial e os fatores ligados a SM evidenciando que a Critósos diagnósticos atuais da síndrome metabólica gravidez é um modelo da SM compensada e sugerem que o diabetes gestacional e a hipergilcemia materna diária devam ser acrescentados aos critérios diagnósticos. / Abstract: In 1988, Reaven described the Syndrome X, a junction of several risk factors for cardiovascular diseases, being the insulin resistance the set point for the establishment of such factors. Many denominations were given to this group of co-morbidities and today it is known as metabolic syndrome. lts study has been difficult by the absence of a consensus for its definition. lts prevalence vanes according to the diagnostic criterion used and with the characteristics of the studíed population, being found mainly in people with central obesity. The prevalence in women varies from 10.7% to 40.5%, and it is a predictor of cardiovascular complications associated with two important nosologic entities concerned with gynecology and obstetrics: the polycystic ovaries syndrome and gestational diabetes. A variety of clinical and physiopathoiogical conditions are frequently associated to it. These are: acanthosis nigricans, non alcoholic fatty tiver disease, microalbuminuria, prothrombotic states (elevation of PAI-1 and fibrinogen leveIs), proinflammatory states (elevation of IL-6, TNF-a, resistin and C-RP leveis), endothelial dysfunction and hyperuricemia. The authors make a revision on the laboratorial diagnosis and the factors Iinked to the metabolic syndrome and attest that pregnancy is a counterbalanced model of the syndrome Critérios diagnósticos atuaiS da 5ifldrOme metabólica and suggest that gestational diabetes and diurnal maternal hyperglycemia should be added to the diagnostic criteria. / Doutor