ResearchPad - gestational-diabetes-diabetes-in-pregnancy-and-in-utero-exposures Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[SUN-644 Effects of Steroid Hormones on Lipogenesis and Insulin Sensitivity - an Insight into the Involvement of the Wnt Signaling Pathway]]> Gestational diabetes mellitus (GDM), a condition in which the state of pregnancy induces the development of diabetes, is characterized by heightened maternal insulin resistance. The levels of sex steroid hormones generally increase during pregnancy. It is thought that imbalance in the levels of steroids like estradiol (E2) and progesterone (P4) with respect to each other, may increase susceptibility towards GDM. To understand the metabolic effects of these steroids, ovariectomized (OVX) rats were treated with E2 or P4 at dosages mimicking the true hormonal status as in pregnancy. E2 significantly reduced the body weight gain (145.4±1.4% to 108.3±0.8%, p<0.001, n≥12) as well as the cumulative food intake (391.3±14.6 g to 312.5±9.0 g, p<0.001) over the course of the 23 day-treatment period. It also decreased the quantity of accumulated gonadal white adipose tissue (GWAT) in the body (3.3±0.2 g to 1.1±0.1 g, p<0.001) and repressed expression of lpl (1.3±0.2 fold, p<0.05) and other lipogenesis markers. P4, on the other hand, enhanced lpl expression (3.7±0.2 fold, p<0.001), but did not affect the total quantity of GWAT. Further, E2 treatment brought about an increase in the expression of insulin sensitivity markers like insr in the GWAT (4.5±0.6 fold, p<0.001) and soleus skeletal muscle (6.2±0.3 fold, p<0.001), as well as an increase in the protein levels of GLUT4.

GDM susceptibility in pregnant women is most commonly associated with SNPs in the tcf7l2 gene, the product of which is an effector of the canonical Wnt signaling pathway. It has also been reported that certain actions of steroid hormones are mediated by Wnt signaling. Moreover, we found that tcf7l2 and other components of this pathway (β-catenin protein, lrp5) were up-regulated following treatments with E2 (3.8±0.2 fold, p<0.001 in GWAT; 5.3±0.2 fold, p<0.001 in soleus) and P4 (2.1±0.2 fold, p<0.05 in GWAT; 2.9±0.3 fold, p<0.001 in soleus). We therefore hypothesized that the metabolic actions of these steroids may be mediated by Wnt signaling. To test this hypothesis, we conducted experiments in which OVX rats treated with steroids as described above, were additionally treated with niclosamide (NIC), a Wnt pathway inhibitor. NIC in conjunction with E2 increased GWAT accumulation and lipogenesis, thereby reversing the action of E2. NIC treatment in OVX rats did not change these parameters, indicating that this effect is specific to the inhibition of Wnt signaling modulated by E2. Additionally, NIC inhibited the E2-modulated increase in insulin sensitivity in GWAT and soleus. Taken together, the results suggest that the actions of E2 on insulin sensitivity and lipogenesis are mediated by the Wnt signaling pathway. No such observation was made with respect to the effect of P4 on lipogenesis. Understanding the mechanistic actions of these steroids may play an important role in devising methods to prevent conditions like GDM before its onset.

<![CDATA[SUN-641 Identifying Risk Factors Associated with Severe Maternal Morbidity Among Women with Gestational Diabetes Using Common Data Model]]> Objective: To identify the risk factors associated with severe maternal morbidity among women with gestational diabetes using common data model

Background: Severe maternal morbidity is an unintended, adverse outcome of the pregnancy or the process of labor and delivery that causes short and long-term consequences to women’s and infants’ health. The prevalence of severe maternal morbidity has been increasing, from 5 to 14 cases per every 1,000 births from 1994 to 2014, and is estimated to increase over time.

Previous studies have shown an association between gestational diabetes and pregnancy complications including hypertension, preeclampsia, and preterm birth. We assessed the association of representative biomarkers with severe maternal morbidity among women with gestational diabetes.

Methods: This cohort study used data collected from common data model database at a single tertiary center in Seoul, Korea during 2004-2019. All patients with indication of gestational diabetes were included in the study. Cases were all women who experienced severe maternal morbidity using the ICD-10 codes identified by the Centers for Disease Control and Prevention. We assessed associations between representative biomarkers and severe maternal morbidity, using t-test and multivariable logistic regression models.

Results: Among 15,096 women who gave birth, the prevalence of gestational diabetes was 9.19% (n=1,388). Among those, 329 (23.7%) developed severe maternal morbidity during pregnancy. HbA1c, triglyceride, and fasting blood sugar were higher among women with severe maternal morbidity (p<0.05) and younger age showed association (p<0.01) with severe maternal morbidity.

Conclusion: This study showed that gestational diabetes was highly associated with severe maternal morbidity. Blood glucose and lipid metabolism were shown to be associated factors with severe maternal morbidity among women with gestational diabetes.

<![CDATA[SUN-629 Text for Success in Gestational Diabetes: Development and User Experience Testing of a Text Messaging Program]]> Background: Gestational diabetes mellitus (GDM) affects 5–10% of pregnancies in the United States. Poorly controlled GDM can lead to serious fetal and maternal complications. Women diagnosed with GDM are asked to form many new self-management habits. Studies have shown that text messaging is an effective, easily accessible way to improve management of diabetes outside of pregnancy, but this method has not been studied in GDM.

Objective: Obtain user feedback and iteratively incorporate it into a personalized text messaging program for women with GDM.

Methods: We performed user experience testing of a text messaging program (Txt4GDM), which was created by a multidisciplinary team based on the Health Belief Model. The program includes: 1) reminders to check blood glucoses sent 4 times per day based on self-reported mealtimes, 2) positive feedback for each blood glucose reported by a user (with an algorithm instructing users to contact their care team if too high/low), 3) one educational message and 4) one motivational message per week.

Women with GDM received simulated messages on a study smartphone. Subjects participated in semi-structured interviews about the content and phrasing of text messages. Interview replies were categorized into themes and used to iteratively optimize the program.

Results: 10 women completed user experience testing. All participants thought the program would be useful for women with newly diagnosed GDM and would use it during their first pregnancy with GDM. There were several features of the program that participants particularly liked, which were categorized into two themes: 1) customization of timing of messages and 2) messages including information not adequately covered in routine care (such as healthy snack ideas and exercise).

Several themes emerged from the semi-structured interviews that were used to optimize the program. 1) Further customization of message timing: We added the ability to enter different mealtimes for weekends and weekdays, which was well-received in subsequent iterations. 2) Minimization of jargon: Multiple women did not know what the “M” in GDM stood for, so we removed “GDM” from the messages. 3) Women wanted the messages to be more specifically related to GDM. For example, an educational message said: “Drinking water, instead of soda or juice, is healthy for you.” The phrase “and can help regulate your blood sugar” was added based on participant feedback.

Conclusions: Overall, women with GDM would use the Txt4GDM text messaging program and think it would be helpful for GDM self-management. Based on user feedback, enhanced customization of timing of text message delivery, minimization of jargon, and language specific to GDM in educational messages were added. We are testing the optimized text messaging program in an ongoing usability study.

<![CDATA[SUN-637 The Impact of Hyperandrogenemia and Western-Style Diet on Post-Pregnancy Metabolism in Nonhuman Primates]]> Polycystic ovary syndrome (PCOS) often is associated with hyperandrogenemia and an increased incidence of obesity and type 2 diabetes. To understand the separate and combined effects of androgens and obesity on reproductive and metabolic parameters, our group established a nonhuman primate model consisting of animals receiving either testosterone (T, mean value of 1.4 ng/mL), an obesogenic western-style diet (WSD, 36% of calories from fat compared to 16% in normal monkey chow), or a combination of T+WSD. T+WSD increased insulin resistance compared to WSD alone after three years of treatment and reduced fertility. Those T+WSD animals that became pregnant had a mild worsening of glucose homeostasis during pregnancy. The current study sought to determine how T+WSD affected post-pregnancy metabolic health and whether T+WSD led to the worsening of insulin resistance after pregnancy. Intravenous glucose tolerance tests (ivGTT) were performed 1) before pregnancy, 2) approximately 3-4 months after C-section, which occurred between gestational day 130-135 (3rd trimester), and 3) one year post C-section. All animal groups tended to show increases in weight, BMI, and body fat percentage after pregnancy. Both WSD groups (WSD and T+WSD) had higher overall weights, BMI, and body fat percentages. Measures of insulin sensitivity such as fasting insulin, glucose, and insulin area under the curves during an ivGTT and homeostatic model of insulin resistance (HOMA-IR) all increased over time, but there were no differences between groups. The lack of treatment effect on measures of insulin resistance may be due to the fact that animals that did not become pregnant had significantly higher indices of insulin resistance. Experimental animals underwent a second round of fertility trials thereby allowing for a comparison of glucose homeostasis for those animals that became pregnant in both the 1st and 2nd trial. The WSD group demonstrated increased fasting glucose and glucose AUC during an early third trimester ivGTT in the second pregnancy compared to the first. The control, T, and T+WSD groups did not show significant differences in glucose homeostasis between the first and second pregnancy. These findings indicate that WSD consumption may increase the risk of worsened glucose homeostasis after pregnancy and during subsequent pregnancies. Testosterone, either in isolation or in combination with WSD, did not appear to have a significant impact on post-pregnancy metabolism or worsen metabolic outcomes in a second pregnancy.

<![CDATA[SUN-636 Gaps in Quality of Delivery of Post-Partum Care in Preconception Counselling for Pregnant Women with Pre-Existing Diabetes at a Large Academic Tertiary Centre]]> <![CDATA[SUN-642 Paracetamol May Increase Cardiac Congenital Malformations Risk in Prediabetic Pregnancy Women]]> <![CDATA[SUN-630 Insulin Pumps Versus Multiple Daily Injections in Type 1 Diabetic Pregnancies]]> <![CDATA[SUN-631 New Therapeutic Targets for Gestational Diabetes Control Impact Insulinization, Birth Weight and Neonatal Morbidities]]> <![CDATA[SUN-643 Potential Contributions of Gut Microbiota-Liver Axis to the Transgenerational Metabolic Reprogramming of Maternal Exercise]]> <![CDATA[SUN-640 Sex-Specific Difference in REG3G Expression Directs the Maintenance of Islet Function in Offspring of Obese Mice]]> <![CDATA[SUN-639 Secretagogin Levels Are Unrelated to Gestational Diabetes Mellitus in a Cohort of Pregnant Women]]> <![CDATA[SUN-638 Perinatal DDE Exposure Disrupts Thermogenesis Early in Development]]> <![CDATA[SUN-632 The Impact of Vitamin D Deficiency on Pregnancy in Type 1 Diabetes]]> <![CDATA[SUN-LB117 Faster Acting Insulin Aspart in Patients With Gestational Diabetes Mellitus - an Early Experience From India]]> <![CDATA[SUN-633 Increased Risk of Gestational Diabetes Mellitus in Egyptian Females Undergoing In Vitro Fertilization in Alexandria]]> <![CDATA[SUN-635 Profiling of Activation Patterns of Placental mTOR in Pregnancies Complicated by Gestational Diabetes Mellitus]]>


The mammalian target of rapamycin (mTOR) couples’ energy and nutrient abundance to cell growth and is critically involved in the onset and progression of diabetes, cancer and ageing. Placental mTOR is involved in nutrient sensing and transfer to the fetus; animal models suggest that placental mTOR is upregulated in pregnancies complicated by hyperglycaemia (1). In this study we investigated expression patterns and activation of placental mTOR and possible effects of gestational diabetes (GDM). Our study consisted of GDM-mothers (n=28) and their offspring and ii) mothers (n=33) with normal pregnancies (non-GDM) and their infants. Total and phospho-mTOR (Ser2448) expression were determined in placental biopsies using either immunoblotting and immunohistochemistry (IHC) analysis. Newborn anthropometric parameters were also determined at delivery. GDM pregnant women presented with higher fasting glucose levels than non-GDM (98.12±22.82mg/dL; 73.61±9.89mg/dL; p<0.001). No significant difference was found in birth weight or baby length between GDM and non-GDM infants. IHC analysis showed that both total and activated mTOR were predominantly expressed in trophoblasts and to a lesser extend in syncytiotrophoblasts, in both GDM and non-GDM placentas. GDM placentas exhibited a higher mTOR H-score (2) compared to non-GDM (p<0.012), and WB analysis showed a higher phosphor-mTOR signal intensity (p=0.047) in the same group, most likely due to increased total mTOR expression. mTOR expression was also increased in both GDM syncytiotrophoblasts and endothelial cells compared to non-GDM (p<0.001) whereas a reduced signal was detected in stromal phospho-mTOR (p=0.004). No difference was found in trophoblasts or endothelial cells between the 2 study groups suggesting that activation of this kinase is tightly regulated and is relatively independent of changes in total kinase levels. Interestingly bivariate correlation analysis identified an extensive network of significant associations in the expression levels of total, phosphor-mTOR and P/T mTOR between trophoblasts, stroma, endothelial and syncytiotrophoblastsin control placental biopsies; this network was significantly disrupted in GDM placentas, identifying a disheveled regulation of placental mTOR activity. In conclusion, placental mTOR/PmTOR expression is differentially regulated across different placental cell types and is sensitive to hyperglycaemia associated with gestational diabetes mellitus.(1)M. Castillo-Castrejon and TL. Powell. Front Endocrinol (Lausanne). 2017; 8: 306. (2) E. Lakiotaki, et al., Scientific Reports 2016; 6, 21252.